Fundamentals of Cell Biology

Chapter 6: The Extracellular

Matrix and Cell Junctions

Chapter Summary: The Big Picture

(1)
Chapter foci:
Examine representative molecules that are
commonly found in the space between cells, the
extracellular matrix, which are highly specialized to
perform distinct functions in the extracellular spaces
and in cellextracellular matrix junctions
Examine the molecules that form direct links
between cells, cellcell junctions, with an
introduction to several different kinds of cellcell
junctions

Chapter Summary: The Big Picture (2)

Section topics:
The extracellular matrix is a complex network
of molecules that fills the spaces between
cells in a multicellular organism
Cells adhere to one another via specialized
proteins and junctional complexes

The extracellular matrix (EM) is a complex

network of molecules that fills the spaces
between cells in a multicellular organism
Key Concepts (1):
The extracellular matrix is a dense network of molecules that
lies between cells in a multicellular organism and is made by
the cells within the network.
The principal function of collagen is to provide structural
support to tissues.
The principal function of fibronectin is to connect cells to
matrices that contain fibrillar collagen.
The principal function of elastin is to impart elasticity to
tissues.

The extracellular matrix (EM) is a complex

network of molecules that fills the spaces
between cells in a multicellular organism
Key Concepts (2):
The principal function of laminins is to provide an
adhesive substrate for cells and to resist tensile
forces in tissues.
Proteoglycans consist of a central protein core to
which long, linear chains of disaccharides, called
glycosaminoglycans (GAGs), are attached.

The extracellular matrix (EM) is a complex

network of molecules that fills the spaces
between cells in a multicellular organism
Key Concepts (3):
The basal lamina is a thin sheet of EM found at the
basal surface of epithelial sheets and at
neuromuscular junctions and is composed of at
least two distinct layers.
Cells express receptors for EM molecules. Virtually
all animal cells express integrins, which are the
most abundant and widely expressed class of EM
protein receptors.

Glycoproteins form filamentous

networks between cells
Collagen provides
structural support to
tissues
Basic unit: coiled
coil
4 classes:Type I-IV

Figure 06.01: Collagen subunits are

assembled into triple-helical coiled coils.

Figure 06.02: Collagens are organized into

four major classes, which vary according
to their molecular formula, polymerized
form, and tissue distribution.

Structure of collagen fibers

3 polypeptide
subunits wrapped in
parallel to form a 300nm-long coiled coil
characteristic repeat
sequence consisting
of glycine-X-Y
Figure 06.03: Schematic diagram of
collagen triple-helical coiled coil (top),
organization of coiled coils within a fibril
(middle), and fibrils in a collagen fiber
(bottom).

Collagen assembly

Figure 06.04: Posttranslational modification and assembly of

procollagen subunits.

Fibronectins connect cells to

collagenous matrices
fibronectin repeats
classified into three
groups - Type I, II, III
mechanism of fiber
assembly unclear but
believed that
fibronectin dimers first
bind to cell surface
receptors called
integrins

Figure 06.05: Two

fibronectin
polypeptides are
covalently linked via
disulfide bonds near
the carboxyl
terminus.

Figure 06.06: The

fibronectin dimer
is secreted in a
folded
conformation that
is stabilized by
interactions
between
fibronectin
repeats I1-5, III2-3
and III12-14.

Elastic fibers impart flexibility to tissues

Elastin is organized
into elastic fibers,
which consist of a
core region enriched
in elastin proteins
surrounded by a
tough coating called a
microfiber (or
microfibrillar) sheath

Figure 06.08: Schematic

representation of relaxed and
stretched elastic fibers.

Current model of elastin fibrilogenesis

Figure 06.09: Seven steps of elastin fiber assembly.

Laminins provide an adhesive

substrate for cells
3 polypeptide
subunits wrapped
together to form a
triple helical coiled
coil
each subunit extends
arms out from the
coil giving rise to a
cross-shaped
structure

Figure 06.10: The three chains of the

laminin molecules are wrapped into a
central core.

Proteoglycans provide hydration to

tissues
provide tensile
strength ensuring EM
is hydrated gel
GAGs
>40 different core
proteins identified
each contains modular
structural domains that
can bind to
components of EM

Figure 06.12: Summary of proteoglycan

structures.

Figure 06.15:
Proteoglycans such as
aggrecan complex
with collagen II fibers
in cartilage.

Hyaluronan is a GAG enriched in

connective tissues
binds to proteoglycan
aggrecan
creates large,
hydrated spaces in
the EM of cartilage

Figure 06.15: Proteoglycans such as

aggrecan complex with collagen II
fibers in cartilage.

The basal lamina is a specialized EM

lies immediately adjacent
to, and in contact with,
many cell types
contains proteins
(collagen IV and
nidogen) found only in
this structure
adopts distinct, sheet-like
arrangement
basement membrane

Figure 06.16: Hemisdesmosomes connect to

the basement membrane, which consists of
the basal lamina and a network of collagen
fibers.
Figure 06.17: The
basement
membrane.
Caption A: The
basement
membrane
appears as a thin
layer of protein
immediately under
epithelial cells.

Most integrins are receptors for EM

proteins
bind to EM proteins and
membrane proteins
expressed on surface of
other cells
principal surface proteins
for holding tissues
together
complex structure
classified into 3
subfamilies based on
subunits

Figure 06.18:
Model of integrin
structure.

Figure 06.19:
Integrins are
organized into
subgroups that share
subunits.

Specialized integrin clusters play

distinct roles in cells
clusters classified into 5
types
composition of cluster
varies depending on
type(s) of integrins in
cluster, type of EM bound
by integrins, degree of
tensile strain imposed on
cluster, location of cluster
in cell, and type of cell in
which cluster forms

Figure 06.21: Five

types of integrin
clusters.

Figure 06.22:
Differences in
shape and
composition in
integrin clusters.

Integrins control a vast range of cellular

functions

Figure 06.23: Summary of integrin cluster components and the cellular

activities they control.

Hemidesmosomes
contain 64 integrin
and link to the IF
network
cell surface junction
found at basal surface
of plasma membrane
of epithelial cells
Figure 06.24: Hemidesmosomes are
specialized structures that form at the
junction of epithelial cells and the
specialized extracellular matrix called
the basal lamina.

Cells adhere to one another via

specialized proteins and junctional
complexes
Key Concepts (1):
Cellcell junctions are specialized protein complexes that
allow neighboring cells to adhere to and communicate with
one another.
Tight junctions regulate transport of particles between
epithelial cells and preserve epithelial cell polarity by
serving as a fence that prevents diffusion of plasma
membrane proteins between the apical and basal regions.
Adherens junctions are a family of related cell-surface
domains that link neighboring cells together.

Cells adhere to one another via

specialized proteins and junctional
complexes
Key Concepts (2):
The principal function of desmosomes is to provide
structural integrity to sheets of epithelial cells by
linking the IF networks of cells.
Hemidesmosomes are found on the basal surface of
epithelial cells, where they link the EM to the IF
network via transmembrane receptors.
Gap junctions are protein structures that facilitate
direct transfer of small molecules between adjacent
cells. They are found in most animal cells.

Cells adhere to one another via specialized

proteins and junctional complexes
Key Concepts (3):
Cadherins constitute a family of cell surface
transmembrane receptor proteins that are
organized into eight groups. The best-known
group of cadherins, called classical cadherins,
plays a role in establishing and maintaining
cellcell adhesion complexes such as the
adherens junctions.

Cells adhere to one another via specialized

proteins and junctional complexes
Key Concepts (4):
Neural cell adhesion molecules (NCAMs) are
expressed only in neural cells and function
primarily as homotypic cellcell adhesion and
signaling receptors.
Selections are cellcell adhesion receptors
expressed exclusively on cells in the
circulatory system. They arrest circulating
immune cells in blood vessels so that they can
crawl out into the surrounding tissue.

Tight junctions form selectively

permeable barriers between cells
junctional complex is
made up of:
tight junction
adherens junction
desmosome

Figure 06.25: The junctional complex is

composed of at least three distinct cellcell junctions.

Tight junctions
3 types of
transmembrane
proteins found in the
tight junction:
claudins, occludins,
and the junctional
adhesion molecule
(JAM)
functions as a
permeability barrier

Figure 06.27:
Tight junctions
are held together
by occludin,
claudin, and
junctional
adhesion
molecules.

Figure 06.28: A
model of fast and
slow transport of
solutes through
tight junctions.

Adherens junction
hold epithelial and
endothelial cells together
resist stress
zonula adherens
adhesive junctions in
synapses
intercalated disks between
adjacent cardiac muscle
cells
junctions between layers of
myelin sheath

Figure 06.30: The

zonula adherens
is part of the
junctional
complex.

Figure 06.31: Each

type of adherens
junction functions
to hold adjacent
cells together
tightly.

Desmosome
thick accumulations of fibrils
running across gap between
two plasma membranes of
epithelial cells
fibrils terminate in electrondense material on cytosolic
side of plasma membrane
electron-dense patches are
connected to filaments in
cytosol of each cell

Figure 06.33: Desmosome

proteins are distributed in the
plasma membrane and a
distinctive double plaque
arrangement at the cell surface.

Gap junctions allow direct transfer of

molecules between adjacent cells
cell-to-cell transport of
ions and small
molecules
connexons
6 connexin
subunits

Figure 06.34: The principal structural

unit of the gap junction is the
connexon, which consists of six
membrane-spanning connexin subunits.

Calcium-dependent cadherins mediate

adhesion between cells
70 structurally-related
transmembrane
proteins
2 properties:
1) bind to calcium
ions to fold properly
(Ca, for calcium)
2) adhere to other
proteins (adherin)

Figure 06.37: Cadherin cytoplasmic

tails are linked to actin filaments via
catenin proteins.

Figure 06.38: As the neural tube is

formed, the apical surface of the neural
plate cells constricts, causing the neural
plate to curve inward.

Calcium-independent NCAMs mediate

adhesion between neural cells

Figure 06.39: NCAMs are

produced as both membranebound and soluble proteins of
different sizes.

Figure 06.40: Strong and

weak cell-cell adhesion.

Selectins control adhesion of circulating

immune cells

Figure 06.41: An illustration

of the rolling stop function
of selectins.