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Mirjana Pavlovic

Bioengineering
A Conceptual Approach
Bioengineering
Mirjana Pavlovic

Bioengineering
A Conceptual Approach
Mirjana Pavlovic
Department of Computer and Electrical Engineering
Florida Atlantic University
Boca Raton, FL, USA

ISBN 978-3-319-10797-4 ISBN 978-3-319-10798-1 (eBook)

DOI 10.1007/978-3-319-10798-1
Springer Cham Heidelberg New York Dordrecht London

Library of Congress Control Number: 2014949238

© Springer International Publishing Switzerland 2015

This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of
the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation,
broadcasting, reproduction on microfilms or in any other physical way, and transmission or information
storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology
now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection
with reviews or scholarly analysis or material supplied specifically for the purpose of being entered and
executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this
publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher’s
location, in its current version, and permission for use must always be obtained from Springer.
Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations
are liable to prosecution under the respective Copyright Law.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication
does not imply, even in the absence of a specific statement, that such names are exempt from the relevant
protective laws and regulations and therefore free for general use.
While the advice and information in this book are believed to be true and accurate at the date of
publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for
any errors or omissions that may be made. The publisher makes no warranty, express or implied, with
respect to the material contained herein.

Printed on acid-free paper

Springer is part of Springer Science+Business Media (www.springer.com)

Illustrated by John Mayfield, undergraduate DIS student at FAU
This book is written in memory
of the shadows of my parents who taught
me that giving is the highest expression
of power.

To MOM and DAD with love

and unforgettable memories.
Thank You Note

This book is product of love and enthusiasm for the rapidly growing field of science
which involves integration of different disciplines, something that I have sensed as
a need at a very early stage of my road less travelled. In trying to develop the par-
ticular subjects/topics/courses at Florida Atlantic University (FAU) within a bioen-
gineering group I have established significant and friendly relationships with a lot
of people which I owe gratitude for this book design, and publication, and hope-
fully, its life in the future. Those are Dr. Zvi Roth, who has initiated the program and
stood by me when it was the most difficult, Drs. Nurgun Erdol and Borko Furht,
Chairmen and big fans of modernization and development of integrated programs,
Dr. Maria Larrondo Petrie, with her encouraging, supportive, and warm friendship,
Dr. Hanqi Zhuang who always believed in me, and most of my colleagues from
Department of Computer Science and Electrical Engineering, at FAU. My graduate
and DIS students and their passion for bioengineering, their work and research that
they have done with me or other mentors, were also strong, supportive, inspiring,
and driving forces during this long journey toward the light. Quite unexpectedly, a
young man with infinite patience and talents, undergraduate DIS/research student,
John Mayfield, was capable of following my thoughts and ideas giving his tremen-
dous input in illustrating this fascinating field: a combination of nature and human
work. He used some existing visualizations as models and guides for each of his
visual elaborations. And finally, all of my friends and family members, especially
my extremely constructively helpful brother, deserve to be mentioned within this
list for encouraging me to get into this adventure. I do hope it will show up useful
to those who the book is purposely written for.

John Mayfield

ix
Abstract

The book reflects the critical principles and basic concepts in bioengineering. It
integrates the biological, physical, and chemical laws and principles enlightening
bioengineering as emerging, novel, complex approach with deep roots in the funda-
mental science. It is a concise review on the critical topics in this field including
both: biological/medical and engineering aspects to it. It should be kept in mind yet,
that the book is not bioengineering itself, but rather the introduction to this subject,
with essential purpose to introduce those who do not have necessary background, to
fundamental biological and physiological principles, that are significantly impli-
cated in bioengineering. Therefore, the physical/chemical properties of cells, the
natural design and function of tissues and organs, along with the main principles of
molecules of life existence, composition, conformation, and interplay within differ-
ent physiological scenarios are described and explained. They are used as the funda-
ment for complex cellular and tissues/organs physiological functions such as
function of heart, neuronal, skeletal muscle, and other cells and tissues: lungs, over-
all circulation, liver, gastrointestinal tract, and kidneys. The emerging concepts of
nanotechnology, drug delivery, biomaterials, scaffolds, biomagnetism, and regen-
erative/cellular therapy are outlined, emphasized, and their status of development
and progress is evaluated. Molecular aspects of life communication and molecular
aspects of bioengineering as a fundamental approach in this field are interrelated
and therefore compared in order to give an insight into fundamental, structural
dimension of this approach and its brilliant natural or scientific solutions. The lead-
ing breakthrough personalities and events are mentioned where appropriate, and
their impact on scientific development of this field, emphasized. The author has
combined her own laboratory experience and data with those of others in order to
give the book, both: monograph and scientific-book character. The book is written
by Dr. Mirjana Pavlovic, M.D., Ph.D., who is teaching these subjects/courses for
engineers and science students, and is highly recommended as a helpful tool along
with any textbook.

xi
Preface

Science is organized knowledge.

Herbert Spencer (1820–1903)

Biological engineering or bioengineering is the application of concepts and methods

of biology to solve real-world problems related to the life sciences and/or the appli-
cation thereof, using engineering’s own analytical and synthetic methodologies and
also its traditional sensitivity to the cost and practicality of the solution arrived at. In
this context, while traditional engineering applies physical and mathematical sci-
ences to analyze, design and manufacture inanimate tools, structures and processes,
biological engineering uses primarily the rapidly developing body of knowledge
known as molecular biology to study and advance applications of living organisms.
In a word, biological engineering is based as well as classical engineering upon:
chemistry, electricity, mechanics, magnetism and life science/medical principles.

What is the Difference Between Bioengineering

and Biomedical Engineering?

Bioengineering: biological engineering, biotechnological engineering, or bioengi-

neering (including biological systems engineering) is the application of concepts
and methods of physics, chemistry, mathematics, and computer science to solve
problems in life sciences, using engineering’s own analytical and synthetic method-
ologies and also its traditional sensitivity to the cost and practicality of the solution(s)
arrived at [1–2]. In this context, while traditional engineering applies physical and
mathematical sciences to analyze, design, and manufacture inanimate tools, struc-
tures, and processes, biological engineering uses the same sciences, as well as the
rapidly developing body of knowledge known as molecular biology to study many
aspects of living organisms. Thus, biological engineering is a science-based disci-
pline founded upon the biological sciences in the same way that chemical engineer-
ing, electrical engineering, and mechanical engineering are based upon chemistry,
electricity and magnetism, and classical mechanics, respectively [3].
Biological engineering can be differentiated from its roots of pure biology or
classical engineering in the following way. Biological studies often follow a reductionist

xiii
xiv Preface

approach in viewing a system on its smallest possible scale which naturally leads
toward tools such as functional genomics. Engineering approaches, using classical
design perspectives, are constructionist, building new devices, approaches, and
technologies from component concepts. Biological engineering utilizes both kinds
of methods in concert, relying on reductionist approaches to identify, understand,
and organize the fundamental units which are then integrated to generate something
new. In addition, because it is an engineering discipline, biological engineering is
fundamentally concerned with not just the basic science, but the practical applica-
tion of the scientific knowledge to solve real-world problems in a cost-effective way.
Although engineered biological systems have been used to manipulate informa-
tion, construct materials, process chemicals, produce energy, provide food, and help
maintain or enhance human health and our environment, our ability to quickly and
reliably engineer biological systems that behave as expected is at present less well
developed than our mastery over mechanical and electrical systems [1].
The differentiation between biological engineering and overlap with biomedical
engineering can be unclear, as many universities now use the terms “bioengineer-
ing” and “biomedical engineering” interchangeably. However, according to Prof.
Doug Laufenberg of MIT, biological engineering (like biotechnology) has a broader
base which applies engineering principles to an enormous range of size and com-
plexities of systems ranging from the molecular level—molecular biology, bio-
chemistry, microbiology, pharmacology, protein chemistry, cytology, immunology,
neurobiology, and neuroscience (often but not always using biological substances)—
to cellular and tissue-based methods (including devices and sensors), whole macro-
scopic organisms (plants, animals), and up increasing length scales to whole
ecosystems. Neither biological engineering nor biomedical engineering is wholly
contained within the other, as there are non-biological products for medical needs
and biological products for nonmedical needs [2].
ABET, the US-based accreditation board for engineering B.S. programs, makes
a distinction between biomedical engineering and biological engineering; however,
the differences are quite small. Biomedical engineers must have life science courses
that include human physiology and have experience in performing measurements on
living systems while biological engineers must have life science courses (which
may or may not include physiology) and experience in making measurements not
specifically on living systems. Foundational engineering courses are often the same,
and include thermodynamics, fluid and mechanical dynamics, kinetics, electronics,
and materials properties.

How Bioengineering Relates to Areas

such as Stem Cell Research?

They are fundamentally interrelated, since stem cells are known to be the building
blocks of entire organism, the “blank chips” with great potential to Trans-
differentiate into different tissues, and so regenerate, repopulate, and recruit new
cells in order to heal the process caused by the initial tissue damage [3]. Here we are
Preface xv

in the tissue engineering area, the subarea of biomedical engineering, where stem
cell application is still debatable in some respect, but the results of which are also
encouraging. The great breakthrough is the discovery and use of adult stem cells,
which can be found and taken out of the human body and used either for classical
transplantation or tissue reparation when necessary. There is a considerable advance
in Computer Aided Tissue Engineering (CATE), where the dimensions of tissue
damage can be determined, and tissue samples designed by the use of stem cells and
scaffolds (the supportive structures made from biocompatible biomaterial), which
are enabling stem cells to differentiate and grow in accordance with original tissue
architecture, leading toward complete and perfect reparation. It is also strengthen by
ink-jet printing system, where the stem cell patterns are layered by dispensing them
through notorious ink-jet cartridge [3]. Stem cells have the capability of self-
renewal, expansion under hypoxic conditions, and multipotency-capacity to differ-
entiate into many directions dependent on the conditions. There are even trials with
cells of an old organ which behave like stem cells when introduced into damaged
one. Stem cell researchers explain that those cells already know their environment
and are well instructed; in fact they memorize how to arrange and to what extent to
grow. This approach is developed by Dr. Anthony Atala and known as “transplanta-
tion without a donor.” A great success of stem cell application is especially noticed
in the disease known as osteogenesis imperfecta, where the bones in children are
extremely fragile, and when applied in early stage of child development they can
dramatically improve their future life. I am personally collaborating with two groups
from Europe, and they have very good results with application of autologous adult
stem cells in acute myocardial infarction and other ischemic diseases.

What are the Discipline’s Main Subareas?

Is it OK to Specialize in Only One of These Areas?

They are really numerous, and I think that each is equally important since either
bioengineering or biomedical engineering has so many subdisciplines which are
interrelated and it is difficult to make strict distinctions. In fact, the heart of these
two disciplines is integrative thinking and as such, involves the ideas for the solu-
tions that are coming from life scientists and engineers at the same time. The first
such “crossing over” happened between Alexander Fleming, who has discovered
Penicillin but did not have the possibility to expand its production, and Howard
Florey, who was a pharmacologist (chemical engineer) and who invented technol-
ogy for Penicillin production using Fleming’s frozen samples [2]. Today, for exam-
ple, for a good Rational Vaccine Design (RVD) you need the interaction of
bioinformatician and immunologist in order to do it well. The first one will do the
data mining and necessary mathematical transformations in order to find the best
possible candidate for the vaccine, while another will lead the bioinformatician
through the field of immunology known as vaccination and finally check it experi-
mentally in the wet-lab. So, the hypothesis is tested and either confirmed or rejected.
Yes, it is OK to specialize in only one of these areas if you understand that the
teamwork is the essential request for successful bioengineering solution.
xvi Preface

What are the Typical Jobs that Engineers

Perform in Industry?

Biological engineers or bioengineers are engineers who use the principles of biol-
ogy and the tools of engineering to create usable, tangible, economically viable
products. Biological engineering employs knowledge and expertise from a number
of pure and applied sciences, such as mass and heat transfer, kinetics, biocatalysts,
biomechanics, bioinformatics, separation and purification processes, bioreactor
design, surface science, fluid mechanics, thermodynamics, and polymer science. It
is used in the design of medical devices, diagnostic equipment, biocompatible mate-
rials, renewable bioenergy, ecological engineering, and other areas that improve the
living standards of societies. In general, biological engineers attempt to either
mimic biological systems to create products or modify and control biological sys-
tems so that they can replace, augment, or sustain chemical and mechanical pro-
cesses. Bioengineers can apply their expertise to other applications of engineering
and biotechnology, including genetic modification of plants and microorganisms,
bioprocess engineering, and biocatalysis.
Because other engineering disciplines also address living organisms (e.g., pros-
thetics in mechanical engineering), the term biological engineering can be applied
more broadly to include agricultural engineering and biotechnology. In fact, many
old agricultural engineering departments in universities over the world have
rebranded themselves as agricultural and biological engineering or agricultural
and biosystems engineering. Biological engineering is also called bioengineering
by some colleges and biomedical engineering is called bioengineering by others,
and is a rapidly developing field with fluid categorization. The main fields of bioen-
gineering, and therefore, the typical jobs that they can find may be categorized as:
• Bioprocess Engineering: Bioprocess Design, Biocatalysis, Bioseparation,
Bioinformatics, Bioenergy.
• Genetic Engineering: Synthetic Biology, Horizontal Gene Transfer.
• Cellular Engineering: Cell Engineering, Tissue Culture Engineering, Metabolic
Engineering.
• Biomedical Engineering: Biomedical Technology, Biomedical Diagnostics,
Biomedical Therapy, Biomechanics, Biomaterials.
• Biomimetics: The use of knowledge gained from evolved living systems to solve
difficult design problems in artificial systems.

How is the Market for Fresh Graduates?

What are the Typical Salaries?

This is developing field in a rapid expansion, so the market is open to fresh gradu-
ates, either at universities, hospitals, or industries. The typical salaries are: $45,000–
$55,000 and within a year can reach even $60,000.
Preface xvii

What are the Hot Research and Development Topics?

One of the greatest is growing organs from patient’s own tissue. A very good exam-
ple of that is the bladder. Clinical trial is going on to collect the data. Great “hit” is
drug delivery through particular vectors, the surface of which has the molecules that
bind to specific receptors on damaged tissues. In that way, drug delivery is targeted
toward only damaged tissue (cancer, inflammation, etc.) and the medication affects
only sick cells without touching normal ones. This enables precise dosage and indi-
vidual targeted therapy. The bioinstrumentation has brought up also incredible solu-
tions such as eradication of cancer cells by using golden nanoparticles in combination
with laser technique. Gene therapy has raised the hope in treatment of hemophilia.
Almost unbelievable, but true, the mouse eye is developed to the certain point in one
experimental trial. The development of mouse micro-brain is one of the greatest
challenges in the development of this field.

What are the Long-Term Challenges and Future Directions?

Since the very first use of stem cells in bioengineering, they have been used with
hope that they can have anti-ageing and life-improvement effect. Is the longevity the
ultimate goal? For those who really live in that hope I think that, as a human race
with defined life we cannot live much longer than we do. But as long as we leave,
we should have a good quality of life. And that for sure, will be better, and therefore
also, somewhat longer. So, let us say that it is the ultimate goal and in my vision that
is on its way to be achieved. It does not mean, of course, that stem cells are the
answer to every question. Their use has also its disadvantages and limitations
dependent on the scenario in question.

What are the Academic Prerequisites (Science and Math,

Software Tools, etc.) and What is the Key Academic
Bottlenecks En Route to Graduation?

In my experience, at least here, at FAU I have found that students with good under-
standing of basic sciences (math, chemistry, and physics) even without any biologi-
cal experience can “conquer” biological knowledge to that extent that they feel very
comfortable in becoming independent in their work. Especially if they are scientifi-
cally oriented and therefore, very resourceful, they can surprise you pleasantly with
problem solving and creativity skills. Both are important for bioengineering and
their own growth. My students were amazingly interested in what they were doing
and therefore their knowledge was/is exceptionally solid.
xviii Preface

What are Typical Topics for Senior Design Projects?

I would say: nanotechnology, rational vaccine design, gene therapy, stem cell appli-
cation, bioinstrumentation, etc.

How Much of the Engineer’s Work is Done

at the “Systems Level” and How Much
at the “Individual Device Level”?

It is really hard to say. I do believe that it goes in parallel, since both directions are
challenging and necessary to be developed, and as long as we as humans are differ-
ent, so there will be those who are interested in one and those who have an interest in
another direction. In that sense, both directions will be and I think they are, devel-
oped with great enthusiasm and intellectual investment. An especially important
application is the analysis and cost-effective solution of problems related to human
health, but the field is much more general than that. For example, biomimetics is a
branch of biological engineering which strives to understand how living organisms,
as a result of the prolonged trial-and-error processes known as evolution, have solved
difficult problems in the past, and to find ways to use this knowledge to solve similar
problems in artificial systems [4]. On the other hand, systems biology seeks to utilize
the engineer’s familiarity with complex artificial systems, and perhaps the concepts
used in “reverse engineering,” to facilitate the difficult process of recognition of the
structure, function, and precise method of operation of complex biological systems
[1, 4, 5, and 6].

Boca Raton, FL Mirjana Pavlovic

References

1. Saltzman MW: Biomedical Engineering. (2009), Cambridge University Press, New York. 2009.
ISBN: 978-0-521-840099-6 (hardback)
2. Pavlovic M (Ed), Balint B: Stem cells and Tissue engineering, Springer New York (2013).
ISBN:978-1-4614-5505-9 (eBook)
3. Berger SA, Goldsmith W, Lewis ER. (Eds): Introduction to Bioengineering (1996), Oxford
University Press, Oxford New York. ISBN:0-19-856516 (Hbk)
4. Vunjak-Novakovic G, Scadden DT: Biomimetic platforms for human stem cell research. (2011)
Cell Stem Cell, 8:252–261.
5. Hall GE, Guyton AC, Textbook of Medical Physiology. (2011) Philadelphia, PA, Sounders
Elesevier, ISBN:978-1-4160-4574-8
6. Pavlovic M, Balint B: Stem Cells and Tissue Engineering. (2013) Springer Briefs in Electrical
and Computer Engineering, Springer NY, ISBN 978-1-4614-5504-2, pp. i–xii, 1–153
Contents

1 Cell Content and Basic Construction .................................................... 1

Cell Content and Basic Construction ........................................................ 2
Introduction: Cell Compartmentalization ................................................. 2
Bioengineering Aspects to Cell Compartmentalization............................ 5
References ................................................................................................. 5
2 The Advanced Architecture of the Cell................................................. 7
The Advanced Architecture of the Cell .................................................... 8
Coulomb Forces: A Simplified View of Bonding ..................................... 10
van der Waals Forces ............................................................................ 14
Cell Energy, Kinetics, Electrolytic Dissociation
and Acid–Base Equilibrium .................................................................. 16
The Henderson-Hasselbalch Equation .................................................. 18
Buffers................................................................................................... 18
Macromolecules of Life ........................................................................ 19
Emphasizing Bioengineering Aspects to Advanced Architecture
of the Cell.................................................................................................. 20
References ................................................................................................. 22
3 Cell Physiology: Liaison Between Structure and Function ................. 23
Cell Physiology: Structure and Function .................................................. 24
Cell Structure and Function .................................................................. 24
Facilitated Transport via Transporters .................................................. 26
Membrane and Action Potential ........................................................... 28
Cell Cycle and Cell Division ................................................................ 28
Types of Cell Division: Meiosis/Mitosis................................................... 29
Importance of Mitosis ........................................................................... 29
Importance of Meiosis .......................................................................... 29
Meiosis in Males: Spermatogenesis ...................................................... 31
Male Puberty ......................................................................................... 31
Meiosis in Females: Oogenia/Oogenesis .............................................. 32
References ................................................................................................. 35

xix
xx Contents

4 Genomics.................................................................................................. 37
Genomics: What Was Behind Human Genome Project? .......................... 37
Emphasizing Bioengineering Aspects to Genomics ................................. 40
Molecular Cloning (DNA) ........................................................................ 42
PCR: Sequence of Events ......................................................................... 44
The Cycling Reactions .......................................................................... 44
References ................................................................................................. 47
5 Proteomics: Enzyme: Structure, Function, Kinetics,
and Engineering Aspects ........................................................................ 49
Proteins: Synthesis, Structure and Function ............................................. 49
How Are the Proteins Made in the Cell? .............................................. 50
Enzymes: Structure, Function and Kinetics of the Reactions ............... 50
Emphasizing Bioengineering Aspects to Proteins and Enzymes .............. 53
References ................................................................................................. 54
6 Communication I: Neural System and Regulation
of Communication................................................................................... 57
The Nernst Potential ................................................................................. 61
Neurotransmitter Signaling ....................................................................... 63
Emphasizing Bioengineering Aspects to Nervous System ....................... 63
References ................................................................................................. 66
7 Communication II (Endocrine Control) ............................................... 67
Communication II: Signal Transduction Pathways
and Endocrine Regulation of Communication .......................................... 67
Chemical Structures of the Three Major Classes
of Human Hormones ................................................................................. 71
Feedback Mechanism for Regulation of Hormone Secretions ............. 76
Emphasizing Bioengineering Aspects to Endocrine Control.................... 76
Some of Bioengineering Solutions Applied
in Hormonal Regulation ........................................................................ 77
References ................................................................................................. 78
8 Communication III (Immunological Control)...................................... 81
Communication III: Immune System and Regulation
of Communication .................................................................................... 82
The Adaptive Immune System: Signaling Mechanism......................... 82
T-Cell Receptor Signaling ..................................................................... 82
Cytokine Signaling................................................................................ 84
Emphasizing Bioengineering Aspect to Immunological
Control and Communication: Engineering Vaccines
and Rational Vaccine Design (RVD) ........................................................ 84
Rational Vaccine Design ........................................................................... 86
Roadblocks Toward RVD...................................................................... 86
The Adaptive Immune System .............................................................. 87
The Humoral Arm of Immunity............................................................ 87
Antibodies ............................................................................................. 88
Contents xxi

B Lymphocytes ..................................................................................... 88
The Cell Mediated Arm of Immunity ................................................... 89
Antigen Presenting Cells....................................................................... 89
The Major Histocompatibility Complex ............................................... 90
Cytotoxic T Cells .................................................................................. 90
Helper T Cells ....................................................................................... 91
Example from Author’s Collaborative Work: RVD for Ebola Virus ........ 91
References ................................................................................................. 93
9 Stem Cells in Regenerative Therapy ..................................................... 95
Organogenesis from Adult Stem Cells and Problems
with Different Tissues ............................................................................... 101
Therapeutic Implications for TCSCs as a New Concept .......................... 102
The Concept of VSEL............................................................................... 103
The Concept of Mesenchymal Stem-Cell
(with Dental Pulp Cells as an Example) ................................................... 106
Mobilization as a New Non-invasive Therapeutic Concept ...................... 109
Emphasizing Bioengineering Aspects to Stem Cell Engineering ............. 110
New Concepts in Adult Stem Cell Research with Development
of New Strategies: Personal Experience in the Light
of Significance of Growing Information ............................................... 110
Directions and Relevant Studies: We and Others...................................... 111
Reprogramming as a Therapeutic Event ............................................... 113
References ................................................................................................. 116
10 Concept of Drug Delivery ....................................................................... 121
Introduction ............................................................................................... 121
Development of Nano-Biotechnologies .................................................... 122
Challenges ................................................................................................. 124
Technologies ............................................................................................. 125
Genetically Engineered Cells for Controlled Drug Delivery .................... 128
Sustained Release Technology .................................................................. 128
Emphasizing Bioengineering Aspects to Drug Delivery:
Achieving Precision .................................................................................. 129
References ................................................................................................. 131
11 Engineering Balances.............................................................................. 133
Engineering Systems................................................................................. 134
Open Systems............................................................................................ 136
Closed Systems ......................................................................................... 138
Closed Systems and Organizational Theories........................................... 138
Closed Systems and Change ..................................................................... 139
Homeostasis .............................................................................................. 139
Mass Balances........................................................................................... 141
Steady State............................................................................................... 141
Equilibrium and Dynamic Equilibrium .................................................... 141
References ................................................................................................. 142
xxii Contents

12 Respiration and Digestion: Bioengineering Basics .............................. 143

Emphasizing Bioengineering Aspects to Respiratory
and Digestive Tract ................................................................................... 151
Modeling the Digestive Tract................................................................ 151
References ................................................................................................. 152
13 Circulation and Lungs ............................................................................ 153
Circulation (Circulating Fluid, Blood Vessels, and Pump) ....................... 153
Viscosity of Blood................................................................................. 154
Circulating Fluid ....................................................................................... 156
Heart Muscle Cells.................................................................................... 160
ECG........................................................................................................... 163
Vascular Compliance and Stiffness ....................................................... 163
Blood Pressure ...................................................................................... 164
Wall Tension ......................................................................................... 164
Building New Organs............................................................................ 166
Growing/Replacement Organs .............................................................. 166
References ................................................................................................. 167
14 Waste Disposal from the Body ............................................................... 169
Introduction ............................................................................................... 169
The Role of Excretory Systems (Kidney and Liver) in Eliminating
Wastes and Toxins and Maintaining the Body Balance ............................ 170
The Concept of Biotransformation ........................................................... 171
Structure of the Renal System................................................................... 172
Regulation of Filtration in Glomerulus ..................................................... 173
Phase I: Filtration in Bowman’s Capsule .............................................. 173
Phase II: Reabsorption in the Proximal Tubule .................................... 175
Phase III: Creation of an Osmotic Gradient in the Loop of Henle ....... 176
Phase IV: Regulating Water and Electrolyte Balance
in the Distal Tubule and the Collecting Duct ........................................ 176
The Concept of Clearance, Excretion in Urine, and Calculation
for Different Solutes.................................................................................. 178
Reabsorption and Secretion in the Tubules Through
Transport Processes............................................................................... 178
Countercurrent Mechanism of Gradient Formation
in the Kidney (Henle’s Loop) ............................................................... 178
Direct Secretion ........................................................................................ 178
Selective Reabsorption .............................................................................. 178
Water Regulation by the Kidneys ............................................................. 178
Release of ADH from the Posterior Pituitary into the Bloodstream ......... 179
The Micturition Reflex .............................................................................. 180
Acid–Base Balance ................................................................................... 180
Renin–Angiotensin–Aldosterone System ................................................. 181
Emphasizing Bioengineering Aspect to Kidney Function ........................ 182
Bladder (Transplantation Without a Donor) Atala.................................... 182
Contents xxiii

Liver: Detoxication and Bill Secretion ..................................................... 183

Biotransformation and Biliary Excretion .............................................. 183
Emphasizing Bioengineering Aspect to Liver Function ........................... 185
Liver Transplantation ............................................................................ 185
References ................................................................................................. 185
15 Biomechanics: Principles........................................................................ 187
Introduction: The Laws of Physics ........................................................... 187
Mechanical Properties of Materials .......................................................... 190
Newton’s First Law ................................................................................... 190
Newton’s Third Law ................................................................................. 191
Elasticity ................................................................................................... 192
Elastic Properties and Young’s Modulus .................................................. 193
Viscosity .................................................................................................... 193
Viscosity Coefficients ............................................................................... 196
Newton’s Theory ....................................................................................... 196
Viscosity Measurement ............................................................................. 198
Units .......................................................................................................... 199
Dynamic Viscosity ................................................................................ 199
Viscoelasticity ....................................................................................... 199
Emphasizing Bioengineering Aspects to Cell Biomechanics ................... 200
Efforts from Kubo Laboratory .............................................................. 200
Efforts by Use of the AFM ................................................................... 201
References ................................................................................................. 202
16 Bioinstrumentation: Basic Information ................................................ 203
Instruments in Medical Practice................................................................ 207
Instruments in the Research Laboratory ................................................... 209
Biosensors ................................................................................................. 210
Lab-on-Chip Devices ................................................................................ 211
Emphasizing Bioengineering Aspect to Biosensors ................................. 214
References ................................................................................................. 215
17 Fundamentals of Bioimaging ................................................................. 217
FC and FACS ............................................................................................ 219
Bioimaging on the Basis of Fluorescence................................................. 219
Magnetic Resonance Imaging ................................................................... 220
Image Processing and Analysis ................................................................ 223
Digitization ........................................................................................... 223
Registration and Segmentation ................................................................. 224
Segmentation......................................................................................... 224
Registration ........................................................................................... 225
Image Enhancement .................................................................................. 225
Emphasizing Bioengineering Aspect to Bioimaging ................................ 226
References ................................................................................................. 228
xxiv Contents

18 What Are Biomaterials? ......................................................................... 229

Emphasizing Bioengineering Aspect to Biomaterials:
Current Examples of Artificial Organs ..................................................... 231
Artificial Organs.................................................................................... 232
Beyond Restoration ................................................................................... 241
References ................................................................................................. 243
19 Nanotechnology: Novel Emerging Concepts ........................................ 245
How Did the “Adventure in Nano-space” Start
and Who Are the Facilitators of This Event? ............................................ 249
Discovery of the Structure of Graphene and Significance
of its Impact on Nanotechnology: Gaim and Novoselov ...................... 250
Nanoparticles in the Nature and How Long the Adventure
in the Nanospace Was? ............................................................................. 251
Fermi Level and Graphene .................................................................... 252
Fermi-Dirac Statistics ........................................................................... 252
Electrical and Thermal Conductivity of Graphene ............................... 253
Physicochemical Aspects of Nanoparticles .......................................... 254
Emphasizing Bioengineering Aspects of Nanotechnology
Important for Medicine ............................................................................. 255
The Current Use of Nanoparticles in Medicine .................................... 255
The Use of Nanoparticles in Cancer Treatment ........................................ 261
Conclusions and Future Directions ........................................................... 263
References ................................................................................................. 263
20 Tissue Engineering Breakthroughs ....................................................... 267
Introduction ............................................................................................... 268
NIH Definition of Tissue Engineering (TE) ......................................... 268
The Pittsburgh Tissue Engineering Initiative Definition ....................... 269
Development and Examples of Tissue Engineering ................................. 270
Medical Technology Breakthroughs ..................................................... 270
Summary and Conlusions on the Role of Stem Cells in TE ..................... 273
Microfabrication of Scaffolds and 3-D Growth of Tissues ................... 274
CATE (Computer Aided Tissue Engineering)
as a Leading Concept ............................................................................ 275
Ink-jet Printing of the Cells and Liquid Scaffolds ................................ 275
Transplantation Without a Donor.......................................................... 276
Other Techniques of Great Relevance for Advance of TE.................... 276
Examples of TE/Cell Therapy Treatments in Development
with Help of Neuralstem Inc (Overview) ............................................. 277
References ................................................................................................. 278
21 Cell Culture in Bioengineering-Working on 3-Dimensional
Culture and Ink-Jet Printing: Regenerative Medicine (RM) ............. 281
Introduction ............................................................................................... 282
3-D Culture ............................................................................................... 283
Ink-Jet Printing of the Cells and Liquid Scaffolds.................................... 284
References ................................................................................................. 287
Contents xxv

22 Magnetism and Magnetobiology: New Undiscovered Horizons? ....... 289

Introduction ............................................................................................... 290
Biomagnetism as a Phenomenon in the Nature
and Possibilities for its Measurement ....................................................... 290
In Vivo Imaging of Intravascularly Injected Magnetically
Labeled Stem Cells ................................................................................... 291
Possibilities of Engineering Targeted Cancer Stem Cell Therapy
Using Principles of Magnetism................................................................. 291
Emphasizing Bioengineering Aspect to Biomagnetism ........................... 296
References ................................................................................................. 297
Chapter 1
Cell Content and Basic Construction

The complexity of the simplest known type of cell is so great

that it is impossible to accept that such an object could have
been thrown together suddenly by some kind of freakish, vastly
improbable, event. Such an occurrence would be
indistinguishable from a miracle.
Michael Denton (1943–)

This first chapter is mostly, informative. It is either recapitulation of your previous

knowledge about cell basics or quite a new field for you, dependent on your educa-
tion, so far. Having in mind that it is a developing field from bioengineering point of
view, you should have your solid visual picture of the cell in your mind. Visualize
whatever is possible, especially what is invisible by naked eye! We all know that if
we don’t see something it does not mean that “entity” does not exist, or will not
emerge once we find the tools to detect it.

© Springer International Publishing Switzerland 2015 1

M. Pavlovic, Bioengineering, DOI 10.1007/978-3-319-10798-1_1
2 1 Cell Content and Basic Construction

Cell Content and Basic Construction

Introduction: Cell Compartmentalization

This book will help you with terminology and meaning of the terms, since it will
facilitate development of a vocabulary after every chapter that you can very effi-
ciently use to either fortify your knowledge or confirm and memorize it. But, do not
only memorize. Always think about the questions beyond the scope and try to find
solutions or look for them. Nobody knows answers to all questions—neither me. It
is in human nature—to be limited and reach the individual plateau in final personal
evolution. We are all different and our plateau levels are different. However, fear
not, thrust yourself and go on! Go on with the questions. You will make a great
move if you ask an intriguing question; you have a chance to change the world with
answer. Fundamentally, maybe. And maybe that will be the question that you will
want to answer within your research work. Don’t be shy to ask for that possibility,
since you might lose it if you don’t. Do always what you really wish and like, since
otherwise you will end up doing what somebody else want and you might not nei-
ther want nor like it. Try to avoid that personal catastrophe, since you live in the
country of great opportunities.
We know that understanding of the life is tightly linked to the understanding of
its cellular and molecular structures and their function, as well as genetic code in
each species. The essential breakthroughs in development of biology are done by
Charles Darwin and Gregor Mendel in nineteenth century. Darwin has proposed his
theory of evolution through natural selection and species adaptation as an
underlying mechanism for survival, while Mendel proposed the concept of
inheritance based on chromosomal interplay during cell division with
mathematical precision. Both have open the door for further consideration of
chromosomal structure which with time escalated into DNA discovery and
confirmation of its structure and determining its function in inheritance.
Introduction: Cell Compartmentalization 3

Today, we know that people live longer than they did in the past. Overall life
expectancy has increased from 50 to almost 80 (1900–2000).
1). The growth and expansion of biomedical engineering is a critical factor in this
extension of life and improvement of health. So, what is the essence of terrestrial
life? If you look into the most active organelle in living cells (animal and plant):
mitochondria and chloroplast you will conclude that it is exchange of the matter
(CO2 produced by animal cells and O2 produced by plant cells) and energy-light or
ATP molecule (cell energy currency) synthesized in the cell.
In order to reach efficient solutions to the problems linked to life, biologist and
bioengineer must work together. They do that through many projects in which biol-
ogy, medical, physics; chemistry and mathematical knowledge are integrated.
Although still difficult to define, bioengineering is revolutionary touching biological
sciences in terms of focusing research toward very specific and precise outcomes
[1–3]. Bioengineering captures a spectrum of different disciplines which all together
function harmonically when needed to comfort the requirements (Biomolecular
engineering, Biochemical engineering, Biotechnology, Nanotechnology,
Biomaterials, Biomechanics, Bioinstrumentation, etc.). By definition, bioengineer-
ing is engineering that is applied to Life science, while biomedical engineering is
focused specifically to human health [1]. Yet, the borderlines are not so strict due to
one important thing: they are mostly based on cell structure and function, or physi-
ology. Therefore, the basic knowledge of the cell is necessary whether you want to
study one or another (Fig. 1.1).
The life starts with the cell. It is either unicellular organism per se, or the physi-
ological unit of multicellular organism [3–10]. It is an open system, border-lined
with membrane [5]. The exchange of matter and energy is taking place through. Cell
function is based upon existence of cellular organelles (compartmentalized part of
the cell). It starts with nucleus as the biggest and significant from reproductive (life
maintaining) point of view, and after that many others including: cilia, flagella and
microfilaments as the smallest ones. Cell membrane is the semipermeable mem-
brane with proteins immersed into phospholipid’s bilayer. It communicates through
pores (mechanical, passive transport) and/or ion channels and different carriers, and
receptors integral proteins (active transport). Non-compartmentalized part of the
cell, in which the organelle are immersed, is called cytosol or cytoplasm.
4 1 Cell Content and Basic Construction

Fig. 1.1 The principle of the balance of the life: communication between plants and animals

Cell has many functions, dependent on its final differentiation stage: It is a

solvent, since it contains water and salts. It is also storage of enzymes, the basis for
signaling mechanisms, reproduction (nucleus), cell respiration and aerobic glycoly-
sis (mitochondria), ATP synthesis (mitochondria and cytosol), protein synthesis
(RER), protein package (SER), translation (ribosomes), package of proteins and
biosynthesis of complex carbohydrate matter (Golgi apparatus), hydrolysis-
degradation of other proteins (lysosomes), catalysis of the conversion of toxic
hydrogen peroxide into water and oxygen (peroxisomes, etc.). Many cells and espe-
cially different cell types are involved in formations of tissues and organs. There are
different tissues and organ systems in the body each of which is designed by nature
to perform different function. Their work is orchestrated by control mechanisms in
the body that keep the organism in the state of either dynamic equilibrium or homeo-
stasis not allowing the body to get out of that energy state and molecular order.
Complexity of organism, especially human, is possible thanks to stem cells which
are during gametogenesis, embryogenesis and fetal period of life differentiating into
distinctive, specialized tissues, and organ cells [3].
Biological systems can form populations, and communities. Group of living
and non-living systems interacting on the same landscape is giving the ecosystem.
A major geographical parts characterized by a particular type of flora and fauna is
called biome. It is deeply influenced by climate.
An International conservation designation given by UNESCO is a Biosphere
[3]. They are created to promote and demonstrate a balanced relationship between
humans and the biosphere.
References 5

Hierarchy of life is again, designed by nature. We are learning about principles

of design and usually precisely put that into laws articulated usually by mathemati-
cal equations. Each equation carries a certain message that can be translated into
speaking language. It is not surprising at all, since we are aware that the cell is
composed of atoms and complex biological molecules that have their physicochem-
ical properties, which can be mathematically defined. Furthermore, the entire organ-
ism with its special organ’s physiology is another aspect of the nature’s design. That
is overall physiology of the body which can also show to be founded on many of
mathematical principles such as Bernoulli’s equation, Henderson–Hasselbalch’s
equation, Flick’s Law, Bohr’s effect, diffusion coefficient, osmotic pressure, oncotic
pressure, filtration pressure, blood pressure, blood vessel resistance, viscosity,
viscoelasticity, etc. [6–10].

Bioengineering Aspects to Cell Compartmentalization

• The skills of engineer and life scientist are complementary. To convert the prem-
ises of molecular biology into new processes to make new products requires the
INTEGRATION of these skills.
• And this INTEGRATION is the ultimate goal of bioengineering, by which the
gap between two fields will be bridged.

References

1. Saltzman, M.W.: Biomedical Engineering. Cambridge University Press, New York (2009).
ISBN 978-0-521-840099-6
2. Pavlovic, M., Balint, B.: Stem Cells and Tissue Engineering. Springer Briefs in Electrical and
Computer Engineering. Springer, New York (2013), pp. i–xii, 1–153. ISBN 978-1-4614-5504-2
3. Berger, S.A., Goldsmith, W., Lewis, E.R. (eds.): Introduction to Bioengineering. Oxford
University Press, Oxford (1996). ISBN 0-19-856516
4. Johnson, A.T.: Biology for Engineers, 1st edn. Taylor & Francis, London (2011). ISBN
0-19-856516
5. Andjus, R.K.: General physiology and biophysics. Modules 1–7. Center for Multidisciplinary
Studies. University of Belgrade, Belgrade, Serbia (2002)
6. Domach, M.M.: Introduction to Biomedical Engineering. Prentice Hall, Upper Saddle River
(2009). ISBN 10: 0-13-602003-8
7. Palsson, B.P., Bhatia, S.N.: Tissue Engineering. Prentice Hall, Englewood Cliffs (2003). ISBN
0130416967
8. Bronzino, J.D. (ed.): The Biomedical Engineering Handbook, vol. 1 & II, 2nd edn. CRC, Boca
Raton (2000). ISBN 0-8493-0461-X
9. Rashidi, H.H., Buehler, L.: Bioinformatics Basics. Applications in Biological Science and
Medicine. CRC, Boca Raton (2000). ISBN 0-8493-2375-4
10. Jones, N.C., Pevzner, P.A.: An Introduction to Bioinformatics Algorithms. Massachusetts
Institute of Technology, Cambridge (2004). ISBN 0-262-10106-8
Chapter 2
The Advanced Architecture of the Cell

Learn from yesterday, live for today, hope for tomorrow. The
important thing is to not stop questioning.
Albert Einstein (1879–1955)

This chapter will introduce you with the detailed cell construction: elements,
­molecules, forces and bonds between them, macromolecules and their functions in
the cells as well as movable, working molecules that are maintaining cell ener-
getic level, being capable of performing specific functions. This entire book is
giving you the overall picture of organ-tissue functions starting from the skin
(integumentary system) that wraps the body as the organ which is separating the
body toward external environment as well as the internal organs the functions of
which are interrelated. In order to understand it, it is necessary to understand
how the nature has designed the construction of the cell, or what does cellular
architecture look like?

© Springer International Publishing Switzerland 2015 7

M. Pavlovic, Bioengineering, DOI 10.1007/978-3-319-10798-1_2
8 2 The Advanced Architecture of the Cell

The Advanced Architecture of the Cell

The structure of the cell gives definitely the chemical context to life, since cell is
water–based solution with elements, molecules, and macromolecules dissolved
within it. This immediately answers the question why bioengineer should have to
understand chemistry, since if he wants to solve the problem by improving some
function in the living system; he has to understand chemical laws and processes.
This aspect of integral thinking is involved in designing new molecules for treating
diseases, such as:
• Liposomes/Doxorubicin and other drug delivery systems
• Non-viral gene therapy
• Plaques removal from Alzheimer’s disease (AD)
• Creating artificial devices
• Nuclear Magnetic Resonance (NMR) spectra, of important biomolecules, etc.
Examples of applied chemistry in bioengineering are numerous, and they are
growing in number every day, especially polymers, for drug delivery systems as we
shall see later on.
A matter consists of chemical elements either in pure form or in combination
called compounds [1]. Compound is bigger and heavier than element. Therefore,
chemistry is fundamental to understanding the life, since life is built up of the mat-
ter. What is the matter that makes life so specific? There are about 25 chemical ele-
ments essential to life among 92 known as naturally occurring [1]. They are
organized in Periodic Chart of elements and designated by symbols or letters.
Biologically, the most important are carbon, oxygen, hydrogen, and nitrogen from
which about 96 % of living matter is built up. There are other biologically impor-
tant elements such as (Ca, P, K, S, Na, Cl, and Mg) that make up remaining 4 % of
an organism’s weight. So called trace elements also need to be present in very low
The Advanced Architecture of the Cell 9

concentrations but are of vital importance (Br, Cr, Co, Cu, F, I, Fe, Mn, Mo, Se, Si,
Sn, V, and Zn). Elements can compose the compounds in a fixed ratio, and with dif-
ferent properties than the elements alone have (Nalco is different than either Na or
Cal). Dependent on the types of bonds and the size of molecules, the compounds
can be micro (water and salt bonds-inorganic matter) and/or macromolecules (C–C
or CONH bonds-organic matter) [2].
The behavior of the element is determined by the structure of the atoms that are
building the element. The atom is the smallest possible unit of matter that retains the
physical and chemical properties of its element. Atoms are tiny particles, not visible
by naked eyes. Atoms of the same element share similar chemical properties. Atoms
are made up of subatomic particles, the three of which—the most stable are: neu-
trons (no charge, neutral), protons (positive charge), and electrons (negative charge).
If an atom is electrically neutral, the number of protons equals the number of elec-
trons, which yields an electrostatically balanced charge. They are further divided in
smaller particles known as subatomic, or elementary particles. Today we know that
hundreds of elementary particles have been discovered (neutrino, mesons, moons,
positrons).
These elementary particles are made up of extremely small particles called
quarks. But the quarks, even so small, have their own organization. According to
Gel Man’s system of symmetry, there are quarks and antiquarks, matter and anti-
matter (of the opposite charge). There are 4 different kinds of quarks which
are = 2/3,–1/3,–1/3, = 2/3 that of the electron charge. The quarks combine to make
different elementary particles. Each meson, for example, can be conceived as the
union of quark and antiquark. Knowing these entities is necessary for example for
development of nanotechnology-nanoparticles that can improve some function in
the body or be of diagnostic or curative importance.
In atom, e.g. element, number of protons is constant while the number of neu-
trons can vary. All atoms of an element have the same atomic number (number of
protons in an atom of particular element). In a neutral atom the number of protons
is equal to number of electrons. The number of protons and neutrons in an atom is
known as mass number. The mass of proton and the mass of neutron are both about
1. The atom of an element which has the same atomic number but different mass
number is called isotope (same number of protons but different of neutrons). Some
isotopes are radioactive. These are instable, with the spontaneously decaying
nucleus, emitting subatomic particles and/or energy as radioactivity. The use of
isotopes in biomedical sciences is of great importance for radioactive labeling of
substances in many assay designs, determination of the age of fossils, etc. [1].
Electrons are also important from many aspects, especially valence electrons
(electrons in the outermost energy shell-valence shell since they tend to fill incom-
plete valence shells by interacting with other atoms. This is the reason for creating
chemical bonds—attractions that hold atoms together. Examples of bonds are: cova-
lent, ionic, metallic, hydrogen, and van der Waals.
10 2 The Advanced Architecture of the Cell

Coulomb Forces: A Simplified View of Bonding

The bonds between atoms hold a molecule together. But what causes bonding? Two
atoms form a bond only if their interaction is energetically favorable, that is, if
energy—heat, for example—is released when the bond is formed. Conversely,
breaking that bond requires the input of the same amount of energy.
The two main causes of the energy release associated with bonding are based on
Coulomb’s law of electric charge:
1. Opposite charges attract each other (electrons are attracted to protons).
2. Like charges repel each other (electrons spread out in space).
Each atom consists of a nucleus, containing electrically neutral particles, or neu-
trons, and positively charged protons (Fig. 2.1). Surrounding the nucleus are nega-
tively charged electrons, equal in number to the protons so that the net charge is
zero. As two atoms approach each other, the positively charged nucleus of the first
atom attracts the electrons of the second atom; similarly, the nucleus of the second
atom attracts the electrons of the first atom. As a result, the nuclei are held together
by the electrons located between them.
This sort of bonding is described by Coulomb’s law: Opposite charges attract
each other with a force inversely proportional to the square of the distance between
the centers of the charges.

( + ) charge · ( - ) charge
Attracting force = constant ·
distance 2

This attractive force causes energy to be released as the neutral atoms are brought
together. This energy is called the bond strength.
When the atoms reach a certain closeness, no more energy is released. The dis-
tance between the two nuclei at this point is called the bond length (Fig. 2.1).
Bringing the atoms closer together than this distance results in a sharp increase in
energy. Why? As stated above, just as opposite charges attract, like charges repel.

The Atom

_
_ Neutron

Proton _
_
+
++ + + + _
+ +
_
+ +

_
_

Fig. 2.1 The scholastic Nucleus

model of the atom: nucleus (Protons and Neutrons)
and shells Electron
Coulomb Forces: A Simplified View of Bonding 11

Fig. 2.2 The changes in

energy, E, that result when
two atoms are brought into
close proximity. At the
separation defined as bond
length, maximum bonding is
achieved

If the atoms are too close, the electron–electron and nuclear–nuclear repulsions
become stronger than the attractive forces. When the nuclei are the appropriate bond
length apart, the electrons are spread out around both nuclei, and attractive and
repulsive forces balance for maximum bonding. The energy content of the two-atom
system is then at a minimum, the most stable situation (Fig. 2.2).
Covalent bonds are chemical bonds between the atoms formed by sharing a pair
of valence electrons (Fig. 2.3). They are strong and good example is H2. In the mol-
ecule, the nuclei are shielded from each other by the two electrons. In the molecule
there is an electrostatically stable configuration for the 2 negatively and 2 posi-
tively charged particles (the electrons and the protons).
An alternative to this type of bonding results from the complete transfer of an
electron from one atom to the other. The result is 2 charged ions: 1 positively
charged, a cation, and 1 negatively charged an anion (Fig. 2.4). Again, the bonding
is based on coulombic attraction, this time between two ions (Fig. 2.4).
The coulombic bonding models of attracting and repelling charges shown in
Figs. 2.4 and 2.5 are highly simplified views of the interactions that take place in the
bonding of atoms. Nevertheless, even these simple models explain many of the
properties of organic molecules.
Ionic bond formed between ions (positive-cations and negative anions) by the
electrostatic attraction after a complete transfer of an electron from the donor atom
to an acceptor (change of transfer). These bonds are strong in crystals but fragile in
the water. Ionic compounds are called SALTS (Fig. 2.5).
The molecular polarity is determined by the position of polar and non-polar
covalent bonds. Strength of these bonds is given in the table (expressed as energy
(GA). The strongest is covalent and the weakest van der Waals forces.
Bonding of the atoms within a molecule (H–H) where the line represents a pair
of shared electrons is known as structural formula. Formula which indicates the
number and type of atoms, but does not reveals the structure is known as molecular
formula. Molecules are building up of two or more atoms held together by covalent
bonds. Compounds are the substances composed of two or more elements com-
bined in a fixed ratio and can have covalent or ionic bonds.
12 2 The Advanced Architecture of the Cell

H H + H H H H H
H atom
H2 molecule, covalent bond
electron stablized
by one nucleus
1s atomic orbital each electron
stabilized by two nuclei

sigma molecular orbital

Attraction
e− e−
e− e−

+ + + + +
Repulsion

Atom 1 Atom 2 Covalently Bonded Molecule

Fig. 2.3 Covalent bonding. Attractive (solid-line) and repulsive (dashed-line) forces in the bond-
ing between two atoms. The large spheres represent areas in space in which the electrons are found
around the nucleus. The small circled plus sign denotes the nucleus

e transfer

e− e− e−

+ + + + +
e−

Atom 1 Atom 2 Cation Anion

Ionically Bonded Molecule

Fig. 2.4 Ionic bonding. An alternative mode of bonding results from the complete transfer of
an electron from atom 1 to atom 2, thereby generating two ions whose opposite charges attract
each other

+ 2D Crystalline
Na Cl Na Cl−
Orientation

Free elements Ionically Bonded

Cl−

Cl−
Na+
3D Crystalline 3D Crystalline
Cl− Latice
Latice
Na+
−
Cl

Fig. 2.5 Two different views of crystalline sodium chloride

Coulomb Forces: A Simplified View of Bonding 13

5 kcal/mol−1

R δ− −
δ+ δ R
O H O
δ+
H
alcohol
two oxygen atoms bonded
over hydrogen atom
Water
hexamer
Methanol
tetramer

Fig. 2.6 Hydrogen bond between alcohol and water molecules

ACID ANION

BASE CATION

Green cicles represent anions, blue circles represent cations,

other colored circles represent neutral molecules;
l, liquid phase; g, gaseous phase. For the gaseous phase over
the aprotic ionic liquid, the representation is purely schematic
and has no implication for the actual degree of aggregation.

PROTIC ANIONIC SOLUTION APROTIC ANIONIC SOLUTION

Fig. 2.7 Solutions: protic and aprotic. For the protic ionic liquids, a dynamic equilibrium exists
between the ionic and dissociated forms: [BH] + X-(l) B (l) + HX (l) B (g) + HX (g)

Metallic bond: Metallic bonding is the type of bonding found in metallic elements.
This is the electrostatic force of attraction between positively charged ions and delo-
calized outer electrons.
Hydrogen bond: formed by the charge attraction when a hydrogen atom covalently
bonded to one electronegative atom is attracted to another electronegative atom.
There is no orbital overlap as it is in covalent bond, so its strength is about ten time
weaker than that of covalent or ionic bonds (Figs. 2.6 and 2.7).
However, they are very important in fixing properties such as:
• Solubility,
• Melting points
• Boiling points
in determining the form and stability of crystal structures. Therefore, they play a
crucial role in biological systems.
14 2 The Advanced Architecture of the Cell

van der Waals Forces

These are weak interactions that occur between atoms and molecules that are very
close together and result from charge asymmetry in electron clouds [3]. These
forces are responsible for the condensation of the gases into liquids, and the freez-
ing of liquids into solid. Functional groups determine the type and strength of these
interactions. There are several types of intermolecular interactions. Thus, ionic
compounds contain oppositely charged particles held together by extremely strong
electrostatic interactions. These ionic interactions are much stronger than the inter-
molecular forces present between covalent molecules (Fig. 2.8).
But, even though CH4 has no net dipole, at any one instant its electron density
may not be completely symmetrical, resulting in a temporary dipole. This can
induce a temporary dipole in another molecule. The weak interaction of these tem-
porary dipoles constitutes van der Waals forces (Fig. 2.9).
All compounds exhibit van der Waals forces. The surface area of a molecule
determines the strength of the van der Waals interactions between molecules. The
larger the surface area, the larger the attractive force between two molecules, and
the stronger the intermolecular forces (Fig. 2.10).

Fig. 2.8 Strong ion–ion

electrostatic interactions in
crystallic form of sodium
chloride

Fig. 2.9 van der Waals

interactions between two CH4
molecules. Unsymmetrical
electron density creates a
temporary dipole
Coulomb Forces: A Simplified View of Bonding 15

A compact, spherical molecule

A long, cylindrical molecule

CH3CH2CH2CH2CH3 H3C CH3

n-pentane
CH3 CH3
larger surface area neopentane
stronger van der Waals
interactions smaller surface area
weaker van der Waals
interactions

Fig. 2.10 Surface area and van der Waals forces

Fig. 2.11 Weaker and stronger forces of attraction affected by polarizability between smaller
(fluorine) and larger atoms (iodine)

van der Waals forces are also affected by polarizability. Polarizability is a

­ easure of how the electron cloud around an atom responds to changes in its elec-
m
tronic environment. Thus, larger atoms, like iodine, which have more loosely held
valence electrons, are more polarizable than smaller atoms like fluorine, which have
more tightly held electrons. Thus, two F2 molecules have little attractive force
between them since the electrons are tightly held and temporary dipoles are difficult
to induce (Fig. 2.11).
A molecule’s biological function is related to the shape. The chemical reactions
make and break chemical bonds (Fig. 2.12).
16 2 The Advanced Architecture of the Cell

Fig. 2.12 The different stabilizing interactions in secondary and tertiary protein structure

 ell Energy, Kinetics, Electrolytic Dissociation

C
and Acid–Base Equilibrium

Cell activities as well as body activities require expenditure of energy. Human gains
energy trough the food that they eat. This energy is stored or expended to sustain
life. All of the chemical reactions in our body result in utilization or accumulation
of the energy [4]. It is important to separate the possibility of reaction occurring
from the rate at which the reaction will proceed. These concepts are related, but
distinct. The role of enzymes (proteins which are specialized to serve as biocatal-
izators, to speed up the chemical reactions in the cells), is essential.
The energy currency of the cells is ATP, organic compound which occurs as an
intermedier in metabolism and thanks to three phosphorus groups the last of which
has the weakest covalent bond, can be hydrolyzed to ADP and Pi releasing energy
needed for cellular processes. Energy is always released from chemical bonds and
required for their formation. From thermodynamic point of view, the overall heat of
formation (enthalpy) is a measure of the order, the amount of energy that is either
consumed or released when for example the water is formed, and is called ΔHf
(25 °C and 1 atm) = ΔH of formation. Heats of formation can be used to calculate
the enthalpy changes of other reactions. Negative indicates exothermic (released E)
and positive-(consumed E) endothermic reaction. The entropy of the system is the
measure of disorder in the system or the amount of energy in the system that cannot
Coulomb Forces: A Simplified View of Bonding 17

be used to work. For any change in the state of the system, a change in entropy or
ΔH can be calculated.
Gibbs free energy (G) is related to both entropy (S) and enthalpy (H). It is actu-
ally a measure of the potential energy of the system, which is a function of enthalpy
and entropy.

DG = DH - TDS

The value of ΔG can be used to predict whether a reaction is favorable/spontaneous

under the given conditions. Most biological reactions have a positive ΔG, so they do
not occur spontaneously. How do the unfavorable reactions proceed? They require
an INPUT of energy, which most often come from the braking of a high-energy
phosphate bond found in as special biochemical called ATP. ATP hydrolysis is ener-
getically favorable while ATP synthesis is not, but it occurs thanks to respiratory
chain of events and proton-motive force or respiratory chains created during cell
respiration. Three essential events are occurring on the inner mitochondrial mem-
brane during mitochondrial respiration:
1. Separation of charges (negative inside—electrons—and positive outside—protons)
2. Synthesis of endogenous water
3. Synthesis of ATP from ADP and Pi on ATP-ases/synthases of the inner mito-
chondrial membrane (Fig. 2.13).
During cell metabolism, the pH (negative logarithm of concentration of hydro-
gen ions) is changing toward basic (higher than 7 which is neutral) or acid level
(lower then 7). Acids are molecules that release protons (H+) when added to aque-
ous solutions, while bases are the molecules that release hydroxyl ions (OH–) when
added to acid solution. Deviation of a patient’s blood pH from its normal value
(which is 7.4, near neutral) is always a sign of serious illness. Variations of pH are
found either in different part of the body or within cellular compartments due to
their different metabolic activities based upon enzymatic content. The equilibrium
constant for the reaction is expressed as:

Fig. 2.13 (a, b) Proton-motive force of the respiratory chain and essential events on the inner
mitochondrial membrane during its formation
18 2 The Advanced Architecture of the Cell

The Henderson-Hasselbalch Equation

éA- ù
pH = pK a + log ë û
[ HA ]
• Lawrence Joseph Henderson (1878–1942) was a talented biochemist, among
many other titles, who spent most of his career at Harvard. He was responsible
for developing the components of the equation after studying equilibrium reac-
tions that took place within blood as a result of respiration (specializing in
“fatigue”). His equation was incomplete without a solid calculations going into it.
• Karl Albert Hasselbalch (1874–1962) was a chemist who studied pH closely. He
also studied blood and reactions that took place with oxygen, to put in the sim-
plest of terms. He eventually modified Henderson’s equation by putting mathe-
matical logs into it creating a solid relationship. The Henderson-Hasselbalch
equation can be used to prepare buffer solutions and to estimate charges on ioniz-
able species in solution, such as amino acid side chains in proteins. Caution must
be exercised in using this equation because pH is sensitive to changes in tem-
perature and salt concentration in the solution being prepared.
Dissociation constant: the equilibrium constant for the decomposition of a com-
plex ion into its components in solution. The smaller the value of K, the lesser the
dissociation of the species in solution. This value varies with temperature, ionic
strength, and the nature of the solvent.

Buffers

1. Buffer solutions consist of either: a weak acid and salt of its conjugate base (e.g.
HF and NaF) or: a weak base and the salt of its conjugate acid (e.g. NH3 and
NH4Cl). Buffer solutions are resistant to pH change despite small additions of
acid or base. Buffer systems are very important in living systems (e.g. constant
blood pH is vital).
2. When H+ is added to a buffered solution, it reacts completely with the weak base
present:

H+ + A− HA or H+ + B HB+
H+ + F− HF or H+ + NH3 NH4+

3. When OH– is added to a buffered solution, it reacts completely with the weak
acid present:

HO + H A H2O + A or HO + H B H2O + B

HO + H F H2O + F or HO + H NH3 H2O + NH3

Coulomb Forces: A Simplified View of Bonding 19

4. Steps (2) and (3) are stoichiometry problems: In step (2), H+ is completely
­consumed, leaving excess A– (or B). In step (3), OH– is completely consumed,
leaving excess HA (or BH+). You must determine which species remain and how
much of each remains in solution. Once [A–] and [HA] are calculated, the pH of
solution can be calculated from the Henderson-Hasselbalch equation:

éA- ù
pH = pK a + log ë û
[ HA ]
5. The pH of a buffered solution will be determined by the ratio [A–]/ [HA], (or [B]/
[BH+]). As long as this ratio remains constant, the pH remains constant. This will
be case if [HA] and [A–], (or [B] and [BH+]) are large relative to [H+] and
[OH–]. Optimum buffering occurs when [A–] = [HA]. In this case, the ratio [A–]/
[HA] is most resistant to pH change when H+ or OH– is added.

éA- ù éA- ù
pH = pK a + log ë û If éë A - ùû = [ HA ] then ë û = 1 and pH = pK a
[ HA ] [ HA ]
The pKa of the weak acid selected for the buffer should be as close as possible to
the desired pH.

Macromolecules of Life

Those are the key classes of molecules that are constructed to LINKING small mol-
ecules. These are mostly members of a more general class of chemicals called poly-
mers which are large molecules formed by bonding of many smaller chemicals,
called monomers, into one long molecule. Because of their large size they are called
macromolecules [5].
1. Nucleotides
The monomer of nucleic acid polymers is called a nucleotide. They are com-
posed of pentose, inorganic phosphate and organic base. Dependent on pentose
(ribose or deoxyribose) and composition of the bases, they will make DNA
(deoxyribose) or RNA (ribose and Uracil instead of Tymine).
2. Nucleotide basis (Cytosine, Guanine, Thymine, and Uracil)
3. Nucleic acids (DNA and RNA)
DNA is double-stranded in a form of double-helix; the process of two single
strands of DNA assembling into double-stranded DNA is called hybridization.
Not every pair of DNA strands can form a double helix. Hybridization can only
occur if the two strands have complementary sequence. Complementary strands
are “mirror images”: each strand contains the same information (although the
strands are not identical) but they are mirror images prepared in special way.
20 2 The Advanced Architecture of the Cell

First, the complementarity strand is pointed into different direction: if one strand
is arranged phosphate to pentose, phosphate to pentose facing upward, then the
complementary strand is perfectly predictable. The basis on the complementary
strand match a particular pattern: A goes with T, C goes with G, G does with C,
and T goes with A. These matches—often called base pairings—are determined
by hydrogen bonding interactions between the nucleotides. It is the hydrogen
bonding of complementary base-pair matching that holds the two DNA strands
together in a stable double helix.
4. Proteins and how they are made?
Proteins are produced by chemical reactions that are directed by DNA. One of
the main functions of DNA in our cells is to provide the information blueprint
for synthesis of the proteins that our cell will need. They are synthesized accord-
ing to central dogma of molecular biology defined by Watson and Crick:
replication, translation, transcription: the language of the bases sequence in DNA
during replication is transcribed by mRNA and translated into the amino-acid
sequence of the protein synthesized on ribosomes in the cytosol. During transla-
tion, the information on mRNA is translated, through series of reactions, into a
linear sequence of amino acids that will become a protein. They can be constitu-
tive proteins of the cell, carriers, messengers, enzymes, antibodies, enzymes.
5. Carbohydrates:
Major source in human diet. According to size: monosaccharides (ribose and
deoxyribose) disaccharides (sucrose) and polysaccharides (starch and cellulose).
(CH2O)n, where n is the number of carbon atoms in the molecule, although there
are the exceptions to this rule.
6. Lipids are not polymers, but fairly large molecules built from a combination of
other simple units.
Triglycerides, phospholipids, and steroids: hydrophobic, hydrophilic, and
amphyphillic.
7. Natural and Synthetic Polymers
Large molecules composed of multiple identical or similar units (monomers)
linked by covalent bonds. DNA and RNA are natural polymers of nucleotides.
Polypeptide is natural linear organic polymer consisted of a large number of
amino acid residues bonded together through peptide (CONH) bond into a chain.
Polysaccharide is a biological macromolecule composed of monosaccharide
subunits. Polymerization is the chemical process of making of a polymer from
a collection of monomers. Polyvinylchloride is synthetic organic polymer used
in biomedical purposes.

 mphasizing Bioengineering Aspects to Advanced

E
Architecture of the Cell

The German scientists used an X-ray beam to scan the internal nanostructure of the
cells, but only blasted them for 0.05 s at a time to avoid damaging the living cells
too quickly [6]. Their method produced images so clear that nanometer-scale
Emphasizing Bioengineering Aspects to Advanced Architecture of the Cell 21

a b
(6R)DDATHF Aminopterin Tetrahydrofolate
Cell Line
(pmol/h/mg prot.)
CCRF-
750 1280 595
CEM
CCRF-
352 447 276
CEM R16

Fig. 2.14 (a) Fluorescent labeling of COX enzyme activity (green) during macrophage phagocy-
tosis of Bacillus Chalmette Gerene (author’s unpublished data). (b) Activity of enzyme FPGS for
different folate and antifolate substrates expressed as pmol/h/mg of protein-published [7]

Fig. 2.15 The effect of

ketamine/xylazine and
ketamine/acepromazine
combinations on 9 L glioma
pH after injection of glucose
as measured by 31P
NMR. The effect of insulin
on 9 L glioma pH following
i.p. injections of ketamine/
xylazine and glucose/Pi. Each
variable represents data
accumulated from three
separate tumour-bearing
rats [8]

structures are visible. The researchers studied living and chemically fixed cells
using the ‘nan diffraction technique’ and when they compared the images of the
cells, the new X-rays prove that the chemical fixing process makes big changes to
tiny 30–50 nm structures in the cell [6]. While the scientists have not speculated on
what the new technique could mean for medical and scientific research, it will make
it possible for experts to study living cells at high resolution and understand a living
cell’ inner mechanics better.
A very new bioengineering aspect emerges from that quite new level, which can
detect living molecules in their natural location and movement.
The author’s work on detection of enzyme activity at fluorescence level and bio-
chemical level are presented in Figs. 2.14a, b [7]. On the other hand, the author’s
experience in “wondering throughout the cell” and looking for pH changes in trans-
planted neural tumor (glioma) under the skin of rat in trying to reach pH changes that
will increase tumor’s radiosensitivity, measured, monitored and detected using NMR,
are presented with result published in British Journal of Cancer in 1996 [8] (Fig. 2.15).
22 2 The Advanced Architecture of the Cell

References

1. Brown, L., Holme, T.: Chemistry for Engineering Students. Mary Finch, Books/Cole, Cengage
Learning, Belmont (2011). ISBN 13:078-1-4390-4791-0
2. Johnson, A.T.: Biology for Engineers, 1st edn. Taylor & Francis, London (2011). ISBN 13:
978-1420077636
3. Andjus, R.K.: General Physiology and Biophysics. Modules 1–7. Center for Multidisciplinary
Studies, University of Belgrade, Belgrade (2002). ISBN 86-80109-11-8
4. Hall, G.E., Guyton, A.C.: Textbook of Medical Physiology. Sounders Elesevier, Philadelphia
(2011). ISBN 978-1-4160-4574-8
5. Shuler, M.L., Karg, F.: Bioprocess Engineering Basic Concepts, 2nd edn. Prentice Hall, PTR,
Upper Saddle River (2002). ISBN 0-13-081908-5
6. http://www.dailymail.co.uk/sciencetech/article-2570300/The-X-ray-living-cell-Breakthrough-
lets-scientists-study-cancer-minute-detail. html#ixzz2upd14slJ
7. Pavlovic, M., Leffer, J., Russello, O., Bunni, M.A., Beardsley, G.P., Priest, D.G., Pizzorno, G.:
Altered transport of folic acid and antifolates through the carrier mediated reduced folate trans-
port system in a human leukemia cell line resistant to (6R) 5,10-Dideazatetrahydrofolic acid
(DDATHF). In: Chemistry and Biology of Pteridines and Folates. Advances in experimental
medicine and biology, vol. 338, pp. 775–778. Springer, New York (1993)
8. Pavlovic, M., Wroblewski, K., Manevich, Y., Kim, S., Biaglow, J.E.: The importance of choice
of anaesthetics in studying radiation effects in the 9L rat glioma. Br J Cancer 74(Suppl. XXVII),
S222–S225 (1996)
Chapter 3
Cell Physiology: Liaison Between Structure
and Function

Nothing in life is to be feared, it is only to be understood.

Now is the time to understand more, so that we may fear less.
Marie Curie (1867–1934)

Cell is the basic functional unit in the body. There are about 200 different ­(specialized)
types of cells in human body, although each is genetically the same. Yet, they are
different in size, shape and function due to the fact that not all the genes and not the
same set of genes are functional or being used in each particular cell type (gene
selectivity). Despite this diversity of cell composition and function, most cells in the
body have the same structural organization. There are between 50 and 200 trillion
of cells in the body of an average person (estimated) and they are constantly being
dividing, metabolizing, working, dying and being replaced by integrated mecha-
nisms. Therefore, structure, morphology, and function are tightly coupled in the cell
giving to each specific cellular entity unique and distinguishable features.

© Springer International Publishing Switzerland 2015 23

M. Pavlovic, Bioengineering, DOI 10.1007/978-3-319-10798-1_3
24 3 Cell Physiology: Liaison Between Structure and Function

Cell Physiology: Structure and Function

Cell Structure and Function

Physiology is defined as the science that treats of the functions of the living ­organism
and its parts, and of the physical and chemical factors and processes involved [1–5].
With respect to that. There are two essential, distinguishable groups of cells that
appear either as unicellular or multicellular organisms.
In prokaryotic cells (typically small, about 1 μ or more), which lack the mem-
brane separated nucleus (but not DNA content needed for replication), cytoskeleton
and cytoplasmic organelles, there is a rigid cell wall, maintaining their shape [3, 4].
In bacteria, peptidoglycan, a polysaccharide that cross links and add to cell stability
is present in the wall. Gram-positive bacteria have predominantly a peptidoglycan
wall, while Gram-negative bacteria have two walls: a thinner, inner wall, containing
peptidoglycan and an outer lipopolysaccharide layer. Despite small size these
organisms are biochemically diverse, with a rapid doubling time. Biomedical engi-
neers often use them for production of recombinant proteins.
Eukaryotic cells (fungi, algae, protozoa, plants and animals) are typically larger,
about 10 μ and more; have a more complex structure with the plasma membrane
consisting of lipid bilayer, separating the intracellular from extracellular space.
Although with a membrane boundary, this is still an open system since it communi-
cates with external world either through pores or different forms of active and pas-
sive transport of molecules and ions [4–7] (Fig. 3.1).
Plant cells have walls to give them structure. Animal cell membrane has elastic
and fluid properties. Around the cell is extracellular matrix (ECM), produced by

Fig. 3.1 Biological systems and energy exchange

Cell Physiology: Structure and Function 25

cells, which holds them together and allows them to form tissues [3, 7, 8]. Specialized
structural molecules are secreted locally by cells and assembled to form a scaffold
that supports cell attachment, spreading, proliferation, migration, and differentia-
tion. Cells influence the chemistry of their surrounding ECM by direct secretion of
molecules, but they also modify the physical characteristics of the matrix locally by
releasing of the enzymes, which can digest or stabilize the gel matrix, or by applica-
tion of physical forces, can physically rearrange the gel components [6–12]. The
composition and organization of macromolecules of the ECM helps determine the
tissue structure and physical properties (examples: the soft cartilage in nose and ear,
the basal lamina sheet underlying epithelial cells (and secreted by epithelial cells)
in the intestine, and tendons, which attach muscles to the bone. Bone contains a
mineral-rich ECM. Proteoglycan, collagen and elastin are the special structural
molecules of ECM, while special adhesives are: fibronectin and laminin [3, 11].
Collagen provides strength, while elastin provides elasticity. Fibronectin serves as a
cross-linker between collagen and GAGs, while laminin also contains binding sites
for cell attachment and promotion of neurite growth [11, 12].
Cell membrane and basic functions: Cell membrane is a semipermeable, lipid
bilayer with proteins immersed into it having very different functions [3, 4]. This
plasma membrane restricts the movement of the water into and out of the cell. The
plasma membrane is described as a fluid mosaic (“model of fluid mosaic”) com-
posed of lipids, carbohydrates, and proteins. In lipid bilayer, amphyphylic phospho-
lipids are arranged with their hydrophobic tails pointing toward the interior of the
membrane and their hydrophilic heads exposed to adjacent water phases, serve as
the main elements of the membrane.
Biomedical engineers have also used lipids to construct devices (for instance:
lyposomes—as drug carriers).
Transport across the cell membrane might capture quite a few mechanisms [3, 5]:
• Diffusion is the spontaneous movement of particles from an area of high concen-
tration to the area of low concentration.
• Passive transport (diffusion): is the process by which water and small uncharged
molecules, such as oxygen (O2) and carbon dioxide (CO2) pass through the
plasma membrane.
• Active transport (facilitated diffusion): process of moving a molecule from an
area of low concentration on one side of the membrane to the area of high con-
centration on the other (against the concentration gradient).
• Osmosis: The diffusion of water through semi-permeable membrane. It is a
physical process in which a solvent moves, without input of energy, across a
semi-permeable membrane (permeable to the solvent).
• Solvent: A solvent is a liquid, solid, or gas that dissolves another solid, liquid, or
gaseous solute, resulting in a more complex solution [2]. The most common
solvent in everyday life is water. Most other commonly-used solvents are organic
chemicals. These are called organic solvents, but not the solute, separating two
solutions of different concentrations.
 Another Random Document on
Scribd Without Any Related Topics
 Intrinsic Value of a Horse.
Although it is a common axiom that "the value of a thing is exactly
what it will fetch," yet in the hunting field the price at which a horse
has been sold is very rarely a criterion of his real worth, the reason
being that his performances are made up of three items, of which he
himself forms only one, the other two being stable management and
good riding, for neither of which is the quadruped entitled to claim
the smallest amount of credit; and yet, on the principle that
"handsome is that handsome does," it is a usual error, especially
among young sportsmen, to estimate that a horse which goes
brilliantly must be a good one, and vice versâ; whereas an ordinary
description of animal, in splendid condition, and judiciously ridden,
cannot fail to leave far behind him a superior one injudiciously
ridden, made up of flesh instead of muscle, of impure instead of
pure blood, and of bloated, unpractised, instead of healthy, well-
exercised lungs. For these reasons it continually happens that a
horse that has been observed to go what is called "brilliantly"
throughout a run, is, at its conclusion, sold for a considerable sum,
in addition to another horse, on which the purchaser, in a few
weeks, leaves behind him the animal he had sold, whose owner now
to his cost discovers that
"The lovely toy so keenly sought
Has lost its charms by being caught"
by him.
But the price of a hunter is materially affected by the quality as well
as the qualifications of his rider, whose position in the world often
confers upon his horses a fictitious value; and accordingly the
hunting stud of the late Sir Richard Sutton—sold by public auction
shortly after his death—realised sums exceeding by at least 40 per
cent. what subsequently proved to be their current value when
transferred to the stables of people of less renown.
Again, a respectable, first-rate horse dealer succeeds in his
profession, not so much by his superior knowledge of the animals he
buys, but by the quantity and quality of the eloquence he exerts in
selling them. Every hunter, therefore, that is purchased from a great
man of this description is necessarily composed of, 1st, his intrinsic
value; and 2nd, of the anecdotes, smiles, compliments, and praises,
which, although when duly mixed up with an evident carelessness
about selling him, captivated the listener to purchase him, like a
bottle of uncorked ardent spirits evaporate, or, like a swarm of bees,
fly away, almost as soon as the transaction is concluded, leaving
behind them nothing but the animal's intrinsic value.
 On Shying.
It often happens that a horse brimfull of qualifications of the very
best description is most reluctantly sold by his master "because he
shies so dreadfully," a frolic which, to a good rider, is perfectly
harmless, and which, if he deems it worth the trouble, he is almost
certain to cure.
A timid horseman, however, not only believes that his horse is
frightened at the little heap of stones at which he shies, but for this
very reason he becomes frightened at it himself; whereas the truth
is that the animal's sensations in passing it are usually compounded
as follows:—
Of fear of {the little heap 1/10.
{whip and spur 9/10.
Now, if this be the case, which no one of experience will deny, it is
evident that the simple remedy to be adopted is, first, at once to
remove the great cause of the evil complained of, by ceasing to
apply either whip or spur; and, secondly, gradually to remove the
lesser cause by a little patient management which shall briefly be
explained.
When a horse has been overloaded with a heavy charge of oats and
beans, which may be termed jumping powder, and primed by a very
short allowance of work, his spirits, like the hair trigger of a rifle, are
prepared on the smallest touch to cause a very violent explosion. In
fact, without metaphor, on the slightest occurrence he is not only
ready, but exceedingly desirous, to jump for joy.
The casus belli which the animal would perhaps most enjoy would
be to meet a temperance run-away awning-covered waggon full of
stout, healthy young women in hysterics, all screaming; or to have a
house fall down just as he was passing it. However, as a great
conqueror, if he cannot discover a large excuse for invading the
territory of his neighbour, is sure to pick out a very little one, so does
the high mettled horse who has nothing to start at, proceed under
his rider with his eyes searching in all directions for something which
he may pretend to be afraid of. Influenced by these explosive
propensities he cocks his ears at a large leaf which the air had gently
roused from its sleep, as if it were a crouching tiger; and shortly
afterwards a fore leg drops under him as suddenly as if it had been
carried away by a cannon shot, because in the hedge beside him a
wren has just hopped from one twig to another nearly an inch.
Now, of course, the effective cure for all these symptoms of
exuberant, pent up spirits is a long, steady hand-gallop up and down
hill across rather deep ground. Before, however, this opportunity
offers, man can offer to the brute beneath him a more reasonable
remedy.
The instant that a horse at a walk sees at a short distance before
him, say a heap of stones, at which he pretends to be or really is
afraid, instead of forcing him on, he should be allowed or, if it be
necessary, forced to stop, not only till he has ceased to fear it, but
until, dead tired of looking at it, he averts his eyes elsewhere.
While advancing towards it, so often as his fear, or pretended fear,
breaks out, by instantly bringing him to a stand-still it should in like
manner be over-appeased.
In slowly passing any object which a horse appears to be afraid of,
the error which is almost invariably committed is to turn his head
towards it, in which case, revolving upon his bit as on a pivot, the
animal turns his hind-quarters from it, and in that position with great
ease shies more or less away from it; whereas, if the rein opposite
to it be pulled firmly, he not only instantly ascertains that his rider's
desire is in opposition to, instead of in favour of forcing him towards
the object of his fear, but when his head is drawn away from it,
although he is able to rush forwards, it is out of his power to shy
laterally.
Now, instead of endeavouring thus to triumph over instinct by
reason, instead of allowing a horse more time even than he requires
to appease his own apprehensions, be they real or pretended, the
course which a gentleman's groom usually adopts is, like giving fuel
to fire, to add to the animal's fear of the object he is unwilling to
approach, his infinitely greater fear of a pair of plated spurs.
The oftener and the stronger this ignorant prescription is applied,
the more violent becomes the disease it undertakes to alleviate,
until, on its being declared to be incurable, the poor frightened
animal is sold for a fault almost entirely created by human hands
and inhuman heels.

The extent to which a timid animal can be appeased by kindness is,

at the present moment, beautifully exemplified by a deer, which has
been so divested of its fears by Tom Hill, the huntsman of the Surrey
fox-hounds, that the animal not only accompanies the hounds when
taken out for exercise, but eats biscuit, and actually sleeps with
them in the kennel.
If, during their meal, two of the hounds fight, by a pat with his fore
feet he tries to separate them. If, at exercise, anything alarms him,
with a bound or two he vaults for safety into the middle of the pack.
And yet, when in this citadel, if any strange dog approaches them,
with malice prepense he rushes out at him, as if determined to kill
him. In short, by kind superintendence the deer has become as fond
of blood-thirsty hounds as they of him.
 Singeing.
As it is incumbent on all civilized communities to be kind to every
living being,—as our laws profess to maintain this Christian axiom,—
and as there exists among us a Society self-constituted for the
especial purpose of "the Prevention of Cruelty to Animals," it would
be very difficult satisfactorily to explain, at least to them, why, in
violation of so benign a theory, we deliberately practise the following
fashions:—

1. Of cutting off all our sheep's tails.

2. Of dittoing the tails of all dogs that take care of sheep.
3. Of dittoing the ears of terriers.
4. Of dittoing a portion of the tails, and occasionally of the ears,
of our horses.
5. Of piercing with a sharp awl the ears of all our daughters, in
order to insert therein golden rings, which, by equalizing all, can
confer no possible benefit on any one: that is to say, provided
Euclid is correct in declaring that "when equals are added to
equals, their sums are equal."

If any person among us defaces a statue, he is liable to punishment

and to the execration of the public; and yet there can be no doubt
that in every sense of the word it is more barbarous to mutilate the
living original of an Almighty Creator than a cold stone or marble
copy thereof, chiselled more or less imperfectly by human hands.
About forty years ago it was the general custom to dock the tails of
all hunters, covert-hacks, and waggon-horses, so close, that nothing
remained of this picturesque, beautiful ornament of Nature but an
ugly, stiff stump, very little longer than the human thumb, which,
especially in summer time, was seen continually wagging to the right
or left, in impotent attempts to brush off a hungry fly, biting the skin
more than a yard off. At about the same period an officer in our
army took to the Cape of Good Hope a gentle, beautiful,
thoroughbred mare, which, to his astonishment, the natives
appeared exceedingly unwilling to approach. The reason was, that
her ears had been cropped; and as among themselves that
punishment was inflicted for crimes, they were induced to infer that
the handsome mutilated animal had suffered from a similar cause—
in fact, that she was vicious.
From the same premises, and by the same reasoning faculties, they
might as erroneously have conceived that the holes bored through
most of the English ladies' ears denoted the existence of a uniform
speck of some sort or other in their characters.
Having briefly enumerated only a few of the mutilations which, in
different regions of the earth, man inflicts, not only upon the animals
around him, but upon himself, we will proceed to notice a
prescription of modern date which has produced very astonishing
results.
As in crime there exists an essential difference between cutting off a
man's head, and cutting off only his hair, so in cruelty does there
exist a similar difference between the fashion which mutilates the
body of an animal, and that which deprives him only of its covering:
still, however, the practice of clipping, shaving, and singeing horses
must, to every person, at first sight appear so incomprehensible that
a slight notice of the subject may possibly be deemed worthy of a
few minutes' consideration.
To a wild horse, roaming in a state of perfect freedom, Nature grants
an allowance very similar to that which every inhabitant of
Grosvenor Square gives to each of his tall powdered footmen:
namely, board, lodging, and two suits of clothing per annum; with
this important difference, however, that while the poor pampered,
gaudy menial is ignorantly dressed throughout the whole year in
cloth and plush of the same thickness, the animal is beneficently
provided with two different descriptions of clothing, namely, a light
thin silky coat for summer wear, and a thick fur one to keep him
warm and comfortable throughout the winter months.
Now it might be expected that if man undertook to interfere with
this provision, he would, in accordance with the spirit and meaning
of the act by which it had been decreed, extend its principle by
relieving the horse of a portion of his covering during the excessive
heat of summer, and by bestowing upon him a little extra warmth in
winter; whereas, by the operation about to be described, he makes
the animal's cold weather coat infinitely less able to resist cold than
that purposely created for sunshine only.
About fifty years ago, during the Peninsular war, it was observed that
the Spanish muleteers gave to the animals they had charge of great
apparent relief by rudely shearing off the hair that covered their
bodies; and on the idea being imported into England, our hunting
men, principally at Melton, commenced the practice by "clipping," at
a cost at first of about five guineas, their hunters.
This operation, which, in its infancy, occupied four or five days, was
succeeded by the practice of shaving, which, in about as many
hours, left the animal as bare as the hide of a pig that had just been
killed, scalded, and scraped.
This latter operation, however, was found to be attended with two
opposite disadvantages: for, if perpetrated too soon, it required to be
repeated, or rather to be succeeded by clipping; and if delayed till
the growth of the thick coat had subsided, the horse remained
throughout the winter naked like an elephant.
In order therefore to shorten the coat exactly in proportion to its
uncertain growth, it was determined gradually and repeatedly to
burn it by fire to the minimum length prescribed, that is, leaving only
sufficient to conceal the bare skin.
When the animal has thus been denuded of his coat, so long as he
remains in his hot stable it is restored to him with compound
interest, by two, and occasionally by three suits of warm clothing,
which he might expect would, like that worn by his lord and master,
be increased as soon as he should be led from his covered domicile
into the open air. But the contrary operation takes place; for while
his owner is swathing himself in his extra flannel hunting clothing,
the singed quadruped at the same moment, in order to be taken to
the meet, at one haul is denuded of the whole of his indoor clothing,
a bridle is put into his mouth, a saddle on his bare back, and in this
state, literally, without metaphor, more naked than he was born, he
is suddenly led or ridden ten or fifteen miles through perhaps wind,
rain, sleet, or snow, to be exposed throughout the whole day to
sudden sweats and sudden chills, in temperatures and at elevations
of the most trying description.
Now, of course, in theory, nothing can be more unnatural, and it
might be added more barbarous, than this treatment; and yet,
strange to say, by acclamation it would be declared by every horse-
owner who has tried it that, in practice, it produces to the animal not
only beneficial, but unexpected, results.
The lungs appear to become stouter.
Hot swelled legs suddenly get cool and fine.
The appetite grows stronger.
The flesh increases.
The muscles thicken.
In consequence of greatly diminished perspiration the amount of
food necessary to recruit the body may be reduced, at least, one
feed per day.
After hunting, the skin, instead of breaking out from internal debility
and exhaustion, remains dry.
Lastly, as mud and dirt cannot take hold of a singed coat, and
consequently as little or no grooming is required, the animal, on
reaching his stable, soon enjoys rest, instead of being for an hour or
two teased, excited, and irritated, by being tied up, hissed at, and
cleaned.
But, against all these advantages, it is only fair to weigh the amount
of suffering which it is supposed by us a horse endures by being
stripped of his coat and clothing, and in that naked state being
suddenly plunged, during winter, into the external air.
In ascertaining this amount of suffering, however, we must not
commit the error of estimating a horse's sensation by what, under
similar circumstances, we imagine would be our own, for the cases
are quite different.
Throughout the frame or fabric of man, his blood, however proud it
may be, circulates so feebly, that on being subjected to a low
temperature it actually, like fluid in a pipe, freezes in his veins;
whereas throughout the body of a horse it is propelled with such
violence, that, like the deep water in the Canada lakes, it is beyond
the power of cold, however intense, to stop it; and accordingly,
when everything else around stands frozen, it triumphantly
continues its fluent course. In fact, the relative power of the two
animals to resist cold is fully proportionate to the difference between
their muscular strength; and as the human being, notwithstanding
its weakness, is strong enough to endure the sudden transition from
a hot bath to a cold one, or, as is the custom in Russia, to a roll on
the snow, so, à fortiori, is a hunter gifted by Nature with a
circulation of blood powerful enough to enable him, without injury or
suffering, to bear an apparently unnatural mode of treatment,
which, although it makes us almost shiver to think of, is productive
to his stouter frame of beneficial results, of inestimable value.
 Meet of the Pytchley Hounds at
Arthingworth.
Among hunting men there is nothing so unpopular as what is called
by the rest of the world a most beautiful, clear, bright day. The
gaudy thing is disagreeable to eyes because it is dangerous to the
bodies to which they respectively belong; for when every twig
glitters in the sunshine, and every drop of dew that hangs upon
them looks like a diamond, the fences so dazzle the eyes of riders,
and especially of horses, that a number of extra falls are very
commonly the result. Soft ground, dull weather, an easterly wind,
and a cloudy sky, form the compound that is most approved of. On
such a day, and under such circumstances, we beg leave to invite
our readers to sit with us patiently for a very few minutes in a
balloon, as, like a hawk hovering above a partridge, it hangs over
the quiet little village of Arthingworth, in Northamptonshire. Those
hounds, headed by that whipper-in riding so lightly and neatly on his
horse, and surrounding their huntsman Charles Payne, jogging
along, seated in his saddle as if he had grown there, are on that
portion of the Queen's highway which connects Northampton with
Market Harborough. They are the Pytchley hounds, the hereditary
property, not of the present master, but of the hunt. They are on
their way from their kennel at Brixworth to a park at Arthingworth to
draw "Waterloo Gorse," which means that every man who intends to
come (and their name is legion) will send there, not his best-looking,
but, what is infinitely better, that which he knows to be "his best
horse," simply because the covert of Waterloo not only usually holds
a good fox, but because it is encircled by very large grass-fields,
enlivened in every direction by the severest fences in
Northamptonshire. See how quietly along every high-road, bye-road,
and footpath, horses and riders, of various sizes and sorts, walking,
jogging, or gently trotting, are converging towards a central point!
Schoolboys are coming to see the start on ponies; farmers on clever
nags; others on young horses of great price; neatly-dressed grooms,
some heavy and some light, are riding, or riding and leading, horses
magnificent in shape and breeding, in the most beautiful condition,
all as clean and well-appointed as if they had been prepared to do
miserable penance in Rotten Row. And are all these noble and
ignoble animals beneath us going to the hunt? Yes, and many more
that we cannot see. Look at those straight streams of white steam
that through green fields are concentrating from north, south, east,
and west upon Market Harborough, from Leicester, from
Northampton, from Stamford, and from Rugby—denoting trains that,
at the rate of thirty or forty miles an hour, are hurrying boxes all
containing hunters for the meet.
On the huntsman and hounds slowly entering and taking up their
positions in the small park at Arthingworth, excepting two or three
farmers, no one is there to receive or notice them. However, in a few
minutes, through large gates and through smaller ones, grooms on
and with their horses walk steadily in; while Charles Payne,
occasionally chucking from his coat-pocket a few crumbs of bread to
his hounds, most of whom are looking upwards at him, leaning over
his horse, is holding confidential conversation with a keeper. "It's too
bad!" whispers an old farmer, who had just been entrusted with the
secret that another fox had last night been shot by poachers; "and,
what's more, it's been a-going on IN MANY WAYS a long time."
"Yes!" replies Charles Payne, looking as calmly and philosophically as
Hamlet when he was moralising over Yorick's skull; "you may rely
upon it that, what with greyhounds,—and poachers,—and traps,—
and poison,—there are very few foxes now-a-days that die a natural
death"—meaning that they were not eaten up alive by the Pytchley
hounds.
But during all this precious time where are all the scarlet coats? Oh!
here they come, trotting, riding, and galloping to the meet from
every point of the compass, and apparently from every region of the
habitable globe, some of the young ones—diverging as usual from
their path of rectitude—to lark over a fence or two. Along the
turnpike and country roads, drags with four horses, light dog-carts
with two, post-chaises and gigs, each laden with men muffled up in
heavy clothing, showing no pink, save a little bit peeping out at the
collar, are all hurrying onwards to the same goal; and as these living
bundles, with cigars in their mouths, are rapidly landing in the park,
it will be advisable that we also should descend there to observe
them.
By about a quarter before eleven the grass in front of the hospitable
hunting-box of one of the late masters of the Pytchley—who, take
him all in all, is one of the very best riders in the hunt—becomes as
crowded as a fair with sportsmen of all classes, from the highest
rank in the peerage down to—not exactly those who rent a 6l.
house,—but who can afford money and time enough to "hoont," as
they call it. While two or three well-appointed servants in livery are
very quietly, from a large barrel, handing glasses of bright-looking
ale to any farmer or groom who, after his long ride, may happen to
feel a little thirsty, and while others from white wicker-baskets are
distributing bits of bread and lumps of cheese to any man who may
feel that beneath his waistcoat there is house-room to receive them,
the honourable and gallant proprietor of the brown barrel and white
baskets, lounging in his red coat, &c., on his exalted lawn, with
sundry small scratches (from bull-finches) on his face, with
something now and then smoking a little from his mouth, and with
that placid and easy manner which in every situation of life
distinguishes him, says to any friend in pink that happens to pass
him, "Won't ye go in for a moment?" But, without invitation, most of
the aristocrats, leaving their horses with their grooms, to ascend a
flight of ladder steps which raises them to the lawn, walk slowly and
majestically across it, adjusting their hair, "just to make their bow."
When that compliment has been paid, they pause for a second or
two in the hall, and then recross the lawn, indolently munching, and
with perfumed handkerchiefs carefully wiping lips or mustachios (as
the case may be), which, if they were very closely approached,
might possibly smell partly of cherries, to proceed to their respective
grooms, and mount their horses.
"Moveon,Sir?" says Charles Payne, in his sharp, quick tone, touching
his cap to the master, who slightly nods to him. "Now-then,-
gentlemen!" he adds, "ware hounds, if you please!" and accordingly,
surrounded by them, onwards he, his two whips, and about two
hundred horsemen, proceed at a walk to cross for nearly half a mile
magnificent fields of grass of from eighty to a hundred acres. As the
Pytchley and Quorn men are, for the reasons we have explained,
each mounted on the very best of their stud, it need hardly be
stated that the lot of horses before us are an accumulation of the
finest specimens in the world; and yet with the highest breeding,
courage, and condition, with magnificent figures, and with bone and
substance sufficient to carry, through deep ground, from twelve to
eighteen stone, there is a calm, unassuming demeanour in their
walk, which it seems almost impossible sufficiently to admire. In like
manner, among the riders, nobody appears to have the smallest
disposition to talk about what he is going to do, or apparently even
to think of where he is proceeding. A man from Warwickshire will
perhaps describe the run he had there on Thursday; while another
will fashionably say to a Leicestershire friend—"Did you do anything
on Friday?"—but most of the field are conversing as they ride along,
not at all about foxes, but about Lords Palmerston, Derby, Italy, the
Pope, &c.
On arriving close to Waterloo Gorse, Charles Payne pulls up to
remain stationary for a couple of minutes, surrounded by his
hounds, who, instead of gazing at his face, are all looking most
eagerly at the covert, until the two whips, getting round it, have
each taken up a position on the other side. "Now-then-little-bitches!"
says Charles, as, with a twitch corresponding with his voice, he
waves forwards his right hand, in which is grasped the silver horn
presented to him by the farmers. Without taking the smallest offence
at the appellation (which after all is a just one, for, as they are the
fastest of his two packs, Charles does not object to bringing them to
"Waterloo"), in they dash; and in a second Charles and his horse are
over the low flight of rails, to gallop along a briary path which
conducts them to a small open space in the centre of the covert. The
greater portion of the field, in coats of many colours, congregate on
its right.
But "quanto sono insensibili questi Inglesi!" Instead of evincing the
smallest degree of anxiety, the conversations we have described are
renewed; and though certainly nobody seems to care the hundred-
thousandth part of a farthing about what his lips are saying, and
though the countenance of every man appears to acknowledge that,
on the whole, he is well enough satisfied with this world, yet men
and horses remain perfectly cool, and occasionally cold, until it might
be fancied by any old soldier standing a mile off that a shell had
suddenly burst in the middle of them. "Pray, don't holla!" exclaims an
old sportsman in a loud whisper. "By Jove, He's Away!" screams a very
young one in pink, pointing to a shepherd who, grasping a struggling
dog with one hand, is holding up his hat with the other. Half a dozen
loud, slow, decisive, monotonous blasts from Charles Payne's horn
are instantly heard, while his hounds, tumbling over each other,
jump almost together over a small hedge and ditch out of the
covert, with their beautiful heads all pointing towards Leicestershire.
As they and reynard take the opposite side of the large grass field in
which the riders had assembled, the start of the latter is very nearly
as sudden as that of the former. Packed together almost as closely
as the wild young creatures that on Epsom course run for the Derby,
the best men and the best horses belonging to the Pytchley, Quorn,
Cottesmore, and Warwickshire hounds start together over turf down
a gentle declivity, at the bottom of which runs an insignificant
stream. Steady horsemanship in every rider is necessary to prevent
treading on those immediately before, or jostling those on each side.
Many a horse, by shaking his head, clearly enough shows how
unwelcome to him is the restraint. From this conglomeration nearly a
dozen men extricate themselves by the superior speed and
management of their horses. Before them[G] is a well-known broad
and strong fence, which, without competing against each other, they
most gallantly charge, "magnâ comitante catervâ," followed by the
great ruck. One,—two,—three,—four,—five,—six men and horses
take it almost together in their stride, and, to the astonishment of
the remainder, all disappear! Every horse had well cleared the broad
ditch on the other side, but all nearly simultaneously had landed in
an artificial bog beyond it, made for draining purposes only a few
days before, and in which the six men and the six horses, each
perfectly unhurt, are now as prostrate and as "comfortable" as if
they had, to use the old nurse's expression, "just been put to bed."
The Hon. Fred. Villiers and Harry Everard are the first over and
down. As they lie together in the mud, looking upwards, they see
coming over the stakes of the hedge the Fitzwilliam girths of the
horses of Henry Forrester and Thomas Atkinson (Vive L'Empereur!),
followed almost instantly by two strangers. However, nearly as
quickly as they all fell, they severally arise, mount their horses, and
gallantly regain the hounds. The field of riders, unable to
comprehend what has happened, and moreover unable as well as
unwilling to stop their horses, as it were by word of command, all
gracefully swerve together in a curve to the right to take two stiff
fences instead of one. About half a dozen, on perfect timber-
jumpers, cross a ditch overhung by a stout ash rail, firmly fixed
between two trees; the remainder break their way through a bull-
finch, and then, throwing their right shoulders forward, at a very
honest pace, all make every proper effort to catch Charles Payne
and the few others who with him had followed the line of the
hounds.
We should certainly tire and jolt our readers very grievously were we
to presume to hustle them through the well-known and splendid run
that ensued. Not only, however, do our limits forbid us to do so, but
as we shall shortly have to quote hunting-anecdotes from a very
superior pen, we willingly pull up to make, in cool blood instead of in
hot, a very few remarks.
[G] This scene we happened to witness.
 Effects Caused by the Sight of Hounds.
A description of a fox-hunt is not very agreeable either to read or to
write,—firstly, because it records a series of events of no very great
importance when they are over; and secondly, because the picture
generally bears the appearance of exaggeration; the reason being,
that it is composed of two parts, one of which it is almost impossible
accurately to delineate. The danger or difficulty which a man and
horse incur in taking any particular leap depends on the one hand
upon the size of the fence, and on the other upon the combined
amount of weight, strength, and activity which the horse can bring
up to it. In trade, if a given weight, whether small or great, be put
into one scale, it can be at once over-balanced by putting a still
greater weight into the other scale. But while the dimensions of a
fence can accurately be measured, it would be not only very difficult
to determine the physical powers of a hunter, but, even if the
statement could be made, ninety-nine people out of every hundred
would most certainly disbelieve it; for, as the old proverb says,
"seeing is believing;" so when a man has ridden a horse across his
farm for many years, he is fully persuaded that,—to use another
common expression,—"he knows what he is made of." But the truth
is, he only knows what he has done, and what he can do under the
maximum of excitement he hitherto has ever experienced; what he
does not know, and indeed what without trial he can have no idea
of, is the enormous amount of latent physical power in his horse
which even the sight of hounds will develop.
For instance, in riding a hack along the road, the confidence or, as it
may be termed, the courage of the rider depends not on himself, but
on the strength and action of the animal he is bestriding. If the nag
picks up his feet quickly, and pops them down firmly—if he goes
stout in his canter and strong in his gallop, his owner rides boldly. If,
however, the very same hero crosses a poor, weak, weedy animal,
with strait action, tripping in all his paces, and with his toes sending
almost every loose stone rolling on before him, he declares the
instant he dismounts that he has been frightened; which difference,
in truth, only means that, on trial, he has satisfactorily and
unsatisfactorily ascertained the physical powers of the first horse to
be amply sufficient, and those of the last totally insufficient, to
perform the given amount of work he requires. Now it is really no
exaggeration to say, that the excitement to a horse caused by the
presence of hounds creates in his physical powers as wide a
difference as exists between those of the two nags just described.
The old, jaded, worn-out, "groggy" hunter, who came hobbling out
of his stable, and who has been fumbling and blundering under his
groom along the road, no sooner reaches the covert side than, like a
lion "shaking the dew-drops from his shaggy mane," he in a moment
casts away the ills which flesh is heir to—in short, his prostrated
powers suddenly revive; and accordingly it is on record, that in one
of the severest runs with stag-hounds ever known in Essex, the
leading horse was aged, twenty-two. Again, on the road, when a
horse has travelled thirty or forty miles, he usually becomes more or
less tired; whereas, during the ten or twelve hours that a hunter is
out of his stable, he will, with the utmost cheerfulness, besides
trotting more than that distance on the road, follow the hounds for
many hours across a heavy country and large fences; and as it is
well known that, in harness, a horse is less fatigued by trotting
before a carriage on a hard macadamized road for forty miles than in
dragging it through an earth road for ten, it would appear almost
fabulous to state how many miles on the road, or especially on dry
turf, could be performed by the amount of excitement, activity, and
strength expended by a hunter during a long and severe day's work.
For the foregoing reasons, if a man during summer rides his hunters,
he will see a variety of fences which, as he quietly ruminates, he will
pronounce to himself to be impracticable, simply because he can
both see and feel that they are greater than the powers he is
bestriding; and yet, when the trees are leafless and the hounds
running, if he happens on the same horse to come to these very
fences, he crosses them without the smallest thought or difficulty—
not because he is excited (for the cooler he rides the better he will
go), but because, while the height and breadth of each fence have
not since he last saw them increased, the physical powers of his
horse, developed by hunting, have been, to say the least, doubled.
The scales which in summer had turned against him now
preponderate in his favour; and accordingly Prudence, who but a
few months before, with uplifted hand, had sternly warned him to
"beware!" with smiling face and joyous aspect now beckons to him
to "Come on!"
The feats which the mere skin and bones of a horse can perform
during hunting are surprising. The comparatively small shin-bone of
his hind legs will, without receiving the smallest blemish, smash any
ordinary description of dry oak or elm-rail, and occasionally shiver
the top of a five-barred gate, and yet, strange to say, though the
frail bone so often fractures the timber, the timber is never able to
fracture the frail bone, which, generally speaking, receives not the
smallest injury from the conflict. Again, when even a singed horse at
great speed has forced his way through a high, strong, spiteful-
looking thorn-hedge, frightening almost into hysterics the poor little
"bull-finch" that is sitting there, he almost invariably passes through
the ordeal with his skin perfectly uncut, and often not even
scratched!—nay, a horse going at great speed may be thrown head
over heels by a wire fence without receiving from it the smallest
blemish!
The trifling facts we have just stated will, we believe, not only
explain the courage and physical powers of a hunter, but the
difficulty of describing to non-hunting readers, without an
appearance of exaggeration, the feats which, during a run, he can
without danger or difficulty perform; for, instead of boasting about a
large fence, it is an indisputable fact that it is infinitely safer for the
horse, and consequently for his rider, than a little one, at which
almost all their worst accidents occur: indeed when a liberal
landlord, for the benefit of his tenants, cuts through their fields a
series of narrow deep drains, to be loosely filled up with earth, it is
good-humouredly said by hunting men, that he is "collar-boning"
them!
And now it is an extraordinary truth that the excitement which the
horse feels in simply witnessing the chase of one set of animals after
another, seems to pervade every living creature on the surface of the
globe. In savage life, the whole object, occupation, and enjoyment
of man, whenever he is not engaged in war, consists in catching and
killing almost any of the creatures that inhabit the wilderness
through which he roams. In a drop of putrid water a microscope
informs us that animalcules of all shapes and sizes, with the same
malice prepense, are hunting and slaying each other. The 600 boys
at Eton, if collected together, would resolve readily among
themselves to receive with decorum, and no doubt with youthful
dignity, any great personages about to honour them with a visit; and
yet, while the grand procession was approaching them, or even just
after it had arrived, if a rat were to run about among them, all their
good intentions in one moment would be destroyed.
During the grand reviews in France of the Allied armies under the
command of Wellington, although the British troops had behaved
steadily enough at Waterloo, it was found that the presence and
authority of "the Iron Duke" were utterly unable to keep them
immoveable as soon as the hares began to jump up among them.
Nay, at Inkerman, while the battle was raging, several men of the
Guards were observed by their officers suddenly to cease firing at
the Russians, who were close to them, in order to "prog" with their
bayonets a poor little scared hare that was running among their feet!
In like manner, although the Anglo-Saxon race are proverbially
phlegmatic (a word described by Johnson to mean "dull; cold;
frigid"), yet no sooner do they hear, in the language of Shakspeare,
"The musical confusion
Of hounds and echo in conjunction,"
than the windows of manufactories are crowded with pale eager
faces, the lanes, paths, and fields become dotted with the feet and
ankles of people of various classes and ages, whose eyes are all
straining to get a glimpse of the run. If Dolly be among them, her
cow, wherever she may be, is quite as curious as herself.
As the fox, who has distanced his pursuers, lightly canters along the
hedge-side of a large grass field, the sheep instantly not only
congregate to stare at him, but for a considerable time remain spell-
bound, gazing in the direction of his course. Herds of bullocks with
noses almost touching the ground, and with long straight tails
slanting upwards, jump sometimes into the air, and sometimes
sideways, with joy. As soon as the hounds appear, the timid sheep
instantly follow them, and accordingly, almost before the leading
rider can make for and get through perhaps the only gap in an
impracticable fence, eighty or a hundred of these "muttons," with
fat, throbbing, jolting sides, rush to and block up the little passage,
in and around which they stand, forming a dense mass of panting
wool, on which no blow from a hunting-whip or from a hedge-stake
produces the slightest effect; and thus the whole field of gentlemen
sportsmen, to their utter disgust, are completely stopped. "I had no
idea," lisps a very young hard-riding dandy, in as feminine and
drawling a voice as he can concoct, "I really hadn't the slightest idea,
before, that sheep were such —— fools!" But their offspring are, in
their generation, no wiser. A poor little lamb, almost just born, the
instant it sees the hounds, will not only leave its mother to follow
them, but under the legs of a crowd of horses—that if they can
possibly avoid it will never tread upon it—canters along, until, its
weak knees and lungs failing, it reels, and is left lying on its side,
apparently dead.
 Cruelty of Hunting Considered.
Over the closed eyes, panting flank, and exhausted frame of this
tiny, innocent, and yet seduced orphan, who had never known its
father, and has just lost its mother, we will venture to offer to our
readers a very few remarks on the strange dissolving view that has
just vanished, or rather galloped, from their sight.

"It's just," said Andrew Fairservice to Frank Osbaldistone,

"amaist as silly as our auld daft laird here and his gomerils o'
sons, wi' his huntsmen and his hounds, and his hunting cattle
and horns, riding haill days after a bit beast that winna weigh
sax punds when they hae catched it."

To the foregoing observation it might also have been added, that in

the extraordinary exertions we have described, the pleasures
enjoyed by the "bit beast" in being hunted, when compared with
those of the two or three hundred animals, human, equine, and
canine, that are hunting him, are as disproportionate as is his weight
when compared to the sum total of theirs.
"No!" said the haughty Countess of —— to an aged huntsman, who,
cap in hand, had humbly invited her ladyship to do him the honour
to come and see his hounds, "No! I dislike everything belonging to
hunting—it is so cruel."
"Cruel!!" replied the old man, with apparent astonishment, "why, my
lady, it can't possibly be cruel, for," logically holding up three fingers
in succession,
"We all knows that the gentlemen like it,
"And we all knows that the hosses like it,
"And we all knows that the hounds like it,
"And," after a long pause, "none on us, my lady, can know for
certain, that the foxes don't like it."
It may strongly be suspected, however, that they do not enjoy being
hunted to death, and consequently that the operation, whenever
and wherever it is performed, is, to a certain degree, an act of
cruelty; which it is only hypocritical to vindicate by pretending to
argue that Puggy has been sentenced to death to expiate his sins;
for if, instead of robbing a hen roost, it had been his habit to come
in all weathers secretly to sit on its nests to help and hatch the
chickens, "The Times" newspaper would have advertised "hunting
appointments" which would have been as numerously attended,—
the hounds would have thrown off with the same punctuality,—and
men and horses would have ridden just as eagerly and as gallantly
to be in at the death of the saint as of a sinner, whose destruction all
barn-door fowls, geese, turkeys, pheasants, and rabbits in his
neighbourhood would certainly not be disposed to regret.
As regards, however, the hunted animal, as well as the creatures
that hunt him, we will observe that the sufferings of a fox that is
eaten up by hounds are probably not much greater and possibly a
little less than those of the poor worm that on our hook catches the
fish,—of the fish that catches the worm,—of the live eels that we
skin,—or of the sheep and bullocks that are every day in thousands
driven foot-sore to our slaughter-houses.
If our Arthingworth fox had taken in "The Times," the Waterloo
covert, after all the preparations we have described, would most
certainly have been drawn "blank." But while undertakers in scarlet,
in black, and in brown coats, were expending many thousand
pounds in preparations for his funeral, he, totally unconscious of
them, was creeping within it, in the rude health and perfect
happiness he had enjoyed in Leicestershire, his native county.
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