Medical Cell Biology

Chapter 2: Cell membrane and

cell surface

Lin Jun
Associate professor
Department of Cell Biology, School of Basic Medicine,
SMU,Guangzhou, China

E-mail: [email protected]
2nd Edition 1
Outline

2.1 Components and structure of cell membranes

2.2 Transmembrane transport

2.3 Cell adhesion molecules and cell junctions

2.4 Extracellular matrix (self-study)

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 1. What is cell adhesion?

• Cell–cell adhesion

Cells in tissues adhere directly to one another.

• Cell-matrix adhesion
Cells adhere to components of the surrounding
extracellular matrix (ECM).

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 2. How do cells adhere to one another or
to the ECM?

• Cell adhesion molecules (CAMs)

Integral membrane proteins to mediate cell-cell or cell-matrix
adhesion by a receptor-ligand binding pattern.

Three models of cell-cell adhesion

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 4. The subtypes of CAMs

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 Cadherins
Ø Biochemical characteristics:
homodimers; Ca 2+-dependent;
Ø Ligands:
Cadherins - cadherins;
Ø Binding pattern:
homophilic binding
Ø Expression pattern:
E-Cadherin in epithelial cell;
N-Cadherin in nerves, muscles, etc.;
P-Cadherin in placenta, epidermis, ets.;
Ø Main functions:
Adhere the same kind of cells to form a tissue;
Compose cell-cell junctions;
Cell rearrangement in embryonic development;
 Integrins
Ø Biochemical characteristics:
Obligate heterdimers;
Divalent cations-dependent;

Ø Ligands:
Integrins - ECM components
(fibronectin, vitronectin, collagen and
laminin, etc.);
Integrins - ICAM

Ø Binding pattern: heterophilic binding;

Ø Main functions:
Mediate cell-ECM adhesion /Compose cell-ECM junction;
Mediate cell-cell adhesion between different kind of cells (WBCs
to endothelia cells).
 Selectins
Ø Biochemical characteristics:
Extracellular Ca 2+ –dependent lectin domains
Ø Ligands:
Selectins - oligosaccharides of glycoproteins or glycolipids
Ø Binding pattern:
Heterophilic binding
Ø Expression pattern:
WBCs (L-selectin),
Platelets (P-selectin),
Endothelia cells (E-selectin)
Ø Main functions:
Collaborate with integrins
when mediate binding of WBC
to blood vessel endothelium.
 Role of E-selectin and integrin in mediating WBC
binding to blood vessel endothelium
E-selectins of the endothelia cells bind to the oligosaccharides on
the WBC surface, which pull down the WBC and activate the
expression of integrins on WBC. Intergins then bind to the ICAM
（a kind of Ig-superfamily CAM）on the endothelia cell, mediating a
strong adhesion of WBC to blood vessel endothelium.

Blood flow

E-selectin

endothelium

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 Ig superfamily CAMs
Ø Biochemical characteristics:
Extracellular multiple immunoglobulin(Ig) domins;
Ca 2+ –independent;
Ø Ligands:
NCAMs (neural CAMs) - NCAMs (homophilic);
ICAMs (Intercellular CAMs) /VCAMs (vascular CAMs)- integrins
(heterophilic);
Ø Binding pattern:
Both homophilic and Heterophilic
Ø Main functions:
Regulate cell adhesion required
for neural system development
(homophilic binding) and immune
response (heterophilic binding).
 Summary on CAMs
Family Ca 2+ Ligands Homophilic / Main functions
depen- Heterophilic
dency binding
Homophilic cell-cell
Cadherins Homophilic
Cadherins Y adhesion; composing
cell-cell junctions

ECM Heterophilic cell-

components , Heterophilic cell/cell-ECM adhesion;
Integrins Y
I-CAM, etc composing cell-ECM
junctions

oligosaccharides Heterophilic Heterophilic cell-cell

Y
Selectins adhesion

Ig The same Homophilic cell adhesion

N kind of CAM Homophilic / in neural development;
superfamily as itself; heterophilic cell adhesion
Heterophilic
CAMs Intergrins in immune response.

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 4. Cell junctions

• Specialized structures formed in cell

membrane to mediate the physical
attachment between cell and cell or between
cell and extracellular matrix;
• Based on cell adhesion, but more
complicated and stable;
• Carry out special functions.

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 Cell Junctions

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 5. Types and characteristics of
cell junctions

v Tight junctions

v Anchoring junctions

v Gap junctions

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 Function: to seal the gaps between
v Tight junction epithelia cells.
Location: Commonly seen in epithelial
cells lining a tube, near apical surface of
the cell.
Composition: Formed by interactions
between strands of transmembrane
proteins on adjacent cells that continue
around the entire circumference of the
cell.

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Transmission (A) and scanning (B) electron
microscope photos showing tight junctions.

Strands
of tight
junction
proteins
Cell 1

Cell 2
 Functions of tight junctions
• Prevent the free passage of molecules through gaps between
epithelia cells ;

• Separate the apical and basolateral domains of plasma

membrane, help establish and maintain cell polarity by
preventing the free diffusion of lipids and proteins.

e.g. the epithelia cells lining small intestine

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 Tight junctions seal the
gaps between epithelia
cells lining small
intestine, thus make
sure the molecules in
lumen of gut can only be
taken into blood by
transmembrane
transport.

Tight junctions prevent

free diffusion of
membrane proteins so
that transporters stay at
the right region to
maintain the one-way
direction of the nutrients
transport.
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 v Anchoring junction

Ø Function: To anchor cells firmly with each other or

with ECM;

Ø Location: tissues that bear tension, such as

epithelium and muscles.

Ø Composition:

Cytoskeletal filaments

Adaptor proteins

Cell adhesion molecules

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 4 Subtypes of anchoring junctions

Actin filaments Intermediate

filaments

Cell-cell Adherens desmosome

junctions
Cell-matrix Focal adhesion hemidesmosome

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 Adherens Junctions
• Locate beneath tight junctions in epithelia cells;
• Form adhesion belt between epithelia cells;
• Involved actin filaments;
•Mediated by cadherins;
•Provide epithelium with contractility and motile force.

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 Focal adhesions
• Locate between cells and ECM;
• Involved actin filaments;
•Mediated by integrins binding to ECM components;
• Connect nonepithelial cells to ECM;
•Transduce adhesion-dependent signals for cell growth and cell motility.

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 • Locate beneath adherens junctions in epithelia cells;
• Involved intermediate filaments;

Desmosome •Mediated by specialized cadherins (desmoglein and

desmocollin);
• Thick cytoplasmic plaques formed by adaptor proteins;
• Provide epithelium with great tensile strength.

Cell 1 Cell 2

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 Hemidesmosomes
• Locate between epithelia cells and ECM;
• Involved intermediate filaments;
• Mediated by integrins binding to ECM components, such as lamina;
• Anchor epithelial cells to underlying tissues such as basal membrane;

Cytoplasm

Intermediate
filaments

Cell membrane

ECM
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 Importance of anchoring junctions:
Without anchoring junctions, tissues are not
able to resist tension or pulling strength.

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 bullous pemphigoid, a skin disorder caused by destroyed
hemidesmosome.

Bullous pemphigoid
is characterized by
the presence of IgG
autoantibodies
specific for some
proteins composing
hemidesmosomes
(BP230 and BP180).
 Summary on anchoring junctions
Types Location CAM Cytoskeleton Functions
involved involved

Adherens Actin Provide

junctions filaments
epithelium with
contractility and
motile force
Cell-cell Cadherins
Provide
Intermediate epithelium with
Desmosome filaments great tensile
strength
Focal
Actin Connect
adhesion filaments nonepithelial
cells to ECM
Cell-ECM Intergrins
Hemidesmoso
Anchor epithelial
me Intermediate
cells to basal
filaments
membrane
 v Gap junctions
Ø Location: present in most cells in animal tissues, near cell bottom;
Ø Composition: 6 connexins (four-pass transmembrane protein)
assemble to form a connexon with an open hydrophilic pore in its
center;

Ø Stucture: 2 connexons
in adjacent cells aligns
with each other to
form a hydrophilic
channel between the 2
cells.

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Classification of gap junction
• Matebolic coupling: allow small molecules (<1000 Dolton) such
as glucose, amino acid, nucleotide, vitamin, cAMP to pass freely.

• Electrical coupling：allow charged ions, such as Ca2+, Na+, K+ to

pass freely.

Function of gap junction

• Create metabolic and electrical coupling between cells.

e.g. Gap junctions between heart muscle cells allow electrical

signal of excitation to spread through the tissue rapidly,
triggering coordinated contraction of heart cells.
 A summary of junctional and nonjunctional adhesive mechanisms

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 Review
Key questions of “cell adhesion molecucles
and cell junctions”:
• What is cell adhesion?
• How is cell adhesion formed?
• What are the functions and characteristics of
each type of cell adhesion molecules (CAMs)?
• What are Cell Junctions?
• What are the special functions and characteristics
of each type of cell Junctions?
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 2.4 Extracellular Matrix
(self-study)

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 2.4.1 Extracellular Matrix
The extracellular matrix (ECM) is a complex meshwork of
proteins and polysaccharides secreted by cells into the
spaces between them. The ECM plays important roles in
cell-cell signaling, wound repair, cell adhesion and tissue
function.
Three major component of ECM

v structure protein

v proteoglycan

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v adhesive protein 33
v Collagens and elastins: structure protein of ECM
Collagen
•water-insoluble fibrous glycoproteins, the backbone
proteins for ECM.
•most abundant protein in the human body (> 25 percent of
all protein) with high tensile strength.
•produced primarily by fibroblasts, and also by smooth
muscle cells and epithelial cells.

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 Structure of Collagens
•Tropocollagen consist of three polypeptide chains (α chain, 1.5nm in
diameter) with repeating motif of Gly-X-Y (Gly-Pro-Hyp or Gly-Lys-Hyl).
•Tropocollagen assemble into collagen fibrils (10-300nm in diameter)
•collagen fibrils aggregates into collagen fibers (several micrometers in
diameter)
 Structural features of collagens
• All collagen molecules are trimers consisting of three
polypeptide chains, called  chains.
• Along at least part of their length, the three
polypeptide chains of a collagen molecule are wound
around each other to form a unique, rod-like triple
helix

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 ◆Assembling of collagen

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v Collagens and elastins: structure protein of ECM

 Elastins
•Water-insoluble proteins rich in glycine and proline;
•Elastic and flexible;
•Present in connective tussues, such as skin, arteries, and
lungs

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 Structure of elastin

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 v proteoglycan: matrix of ECM
core protein + glycosaminoglycans (GAGs)

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Glycosaminoglycans
• a repeating disaccharide
with a -A-B-A-B-A-
structure

• disaccharides include∶

chondroitin sulfate

hyaluronic acid

keratan sulfate

heparan sulfate
…..
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hyaluronic acid
a nonsulfated GAG, assemble proteoglycans into huge
complexes by linkage of the core proteins.

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v adhesive proteins

Fibronectin (FN)
RGD motif (for integrin binding) mediate cell
adhesion to ECM.

Laminin (LN)
Key structural component of basal lamina, a
specialized ECM

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 Fibronectin (FN)

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Laminin (LN)
 2.4.2 Connecting Cells to the ECM

The components of the ECM, such as fibronectin, laminin, proteoglycans,

and collagen are capable of binding to receptors situated on the cell surface.
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 2.4.2 Connecting Cells to the ECM

• The ECM interacts with the surface of the cell

through fibronectin

• Cells attach to the ECM by means of integrins

• Integrins are receptor proteins which are of

crucial importance

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 the integrins binding to RGD motif
(Arg-Gly-Asp) in Fibronectin

The most important family of receptors that attach cells to their

2020-2-26 extracellular microenvironment is the integrins. 48
Basement membrane (Basal lamina)
a specialized ECM structure underlies the epithelium,
which lines the cavities and surfaces of organs.

Structural components:

• laminin：main component, organizer

• Ⅳ type collagen

• entactin

• perlecan
Structure of basement membrane