(ECM)"

Extra Cellular Matrix (ECM)"

The Extra Cellular Matrix: ECM

Extra Cellular: outside the cell, which explains where
the matrix is located. Matrix: structure made from a
network of
interacting components
Component:
fibrous proteins and glycosaminoglycans (GAGs)
Components of the ECM are produced intracellularly by
resident cells, and secreted into the ECM via exocytosis.

Extracellular matrix (ECM)

The extracellular matrix (ECM) is a collec?on
of extracellular molecules secreted by cells
that provides structural and biochemical
support to the surrounding cells.

Surrounds cell
Provides mechanical support
Controls the flow of nutrients
and signals to the cells
Consists of
Fibrous: collagen,
elastin, fibronectin, laminin
Non-fibrous: Proteoglycans
04/19/10
and polysaccharides

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Examples of extracellular matrix

Sheets of epithelial cells rest on a
thin layer of extracellular matrix
called a basal lamina.

Beneath the basal lamina is loose
connec?ve ?ssue, which consists
largely of extracellular matrix
secreted by broblasts.

The extracellular matrix contains
brous structural proteins
embedded in a gel-like
polysaccharide ground substance.

Extracellular components and connec?ons

between cells help coordinate cellular ac?vi?es
Most cells synthesize and secrete materials that
are external to the plasma membrane
These extracellular structures include:
Cell walls of (plants, arthropods and fungi) ECM
The extracellular matrix (ECM) of animal cells
Intercellular junc?ons

Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

The Extracellular Matrix (ECM)

In plants, the ECM is primarily composed of cellulose.

In arthropods and fungi, the ECM is largely composed of chi:n.

In vertebrates, the ECM is made of a complex mixture of
carbohydrates and proteins (plus minerals in the case of bone).

Cell Walls of Plants

The cell wall is an extracellular structure that
dis?nguishes plant cells from animal cells
Prokaryotes, fungi, and some pro?sts also have
cell walls
The cell wall protects the plant cell, maintains its
shape, and prevents excessive uptake of water
Plant cell walls are made of cellulose bers
embedded in other polysaccharides and protein
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

The Extracellular Matrix (ECM) of Animal Cells

Animal cells lack cell walls but are covered by an

elaborate extracellular matrix (ECM)
The ECM is made up of glycoproteins such as
collagen, proteoglycans, and bronec:n
ECM proteins bind to receptor proteins in the
plasma membrane called integrins

Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Bacterial Cell Walls

pep:doglycan

The rigid cell walls of bacteria determine cell

shape and prevent the cell from burs?ng as a
result of osmo?c pressure.

Gram-nega?ve bacteria (such as E. coli):

- a dual membrane system,
- thin cell walls (between inner &outer membranes

Gram-posi?ve bacteria (human pathogen
Staphylococcus aureus):
- a single plasma membrane,
- surrounded by a much thicker cell wall.

The cell walls of eukaryotes (including fungi, algae, and

higher plants) are composed principally of
polysaccharides.

The basic structural polysaccharide of fungal cell walls/
exoskeleton of arthropods is chi:n (a polymer of N-
acetylglucosamine residues)

The cell walls of most algae and higher plants are
composed principally of cellulose. Cellulose is a linear
polymer of glucose residues, oUen containing more than
10,000 glucose monomers.

Chi?n is a linear polymer of N-acetylglucosamine residues,

Cellulose is a linear polymer of glucose.

Model of a plant cell wall

The structure and func?on of cell walls change as plant cells develop.
The walls of growing plant cells (called primary cell walls) are rela?vely thin and
exible, allowing the cell to expand in size.

Once cells have ceased growth, they frequently lay down secondary cell walls
between the plasma membrane and the primary cell wall.
Such secondary cell walls, which are both thicker and more rigid than primary
walls, are par?cularly important in cell types responsible for conduc?ng water
and providing mechanical strength to the plant.

Primary and secondary cell walls dier in composi?on as

well as in thickness.
Primary cell walls: cellulose, hemicelluloses, & pec?ns.
Secondary walls (more rigid) : generally lack pec?n and
contain 50 to 80% cellulose.
Many secondary walls are further strengthened by
lignin, a complex polymer of phenolic residues that is
responsible for much of the strength and density of
wood

How the cell wall helps coordinate cellular

activity
Protects the plant cell
Maintains its shape
Prevents excessive uptake of water

Extracellular Structures
Extracellular matrix (ECM)
-Surrounds animal cells
-Composed of glycoproteins and fibrous
proteins such as collagen
-May be connected to the cytoplasm via
integrin proteins present in the plasma
membrane

16

The animal extracellular matrix includes the

inters??al matrix and the basement membrane.

Inters??al matrix is present between various animal
cells (i.e., in the intercellular spaces)-fills spaces between
cells

Gels of polysaccharides and brous proteins ll the

inters??al space and act as a compression buer
against the stress placed on the ECM.

Basement membranes are sheet-like deposi?ons of
ECM on which various epithelial cells rest- closely
associated with cell surfaces

Extracellular Spaces Extracellular Matrix

Animal cells - glycoproteins

Ex. collagen

ECM cell communication, movement

Connective Tissue underlying an epithelium

Fibroblast, primary cell secreting ECM

Extracellular Matrix Components

The extracellular matrix has three major
components:

- Highly viscous proteoglycans (heparan
sulfate, keratan sulfate, chondroi?n
sulfate), which cushion cells
- Insoluble collagen bers, which provide
strength and resilience
- Soluble mul?adhesive extracellular matrix
proteins (bronec?n, laminin), which bind
proteoglycans and collagen bers to
receptors on the cell surface

Components of ECM
22

Components of the ECM

Collagen
Most abundant glycoprotein (about half of the total protein in the
body).
Forms strong fibers outside of the cell.
Fibers are embedded in a network made of proteoglycans.

Proteoglycans
Collagen fibers are embedded in a network made from proteoglycans.
Are another class of glycoproteins that consists of a small core
protein with many carbohydrate chains covalently attached.
Large complexes can form when hundreds of proteoglycans become
non-covalently attached to a single long polysaccharide molecule.

Components (cont.)
Fibronectin

Glycoprotein that attaches the ECM to the cell itself.

Binds to cell surface receptors called integrins, which are
built into the plasma membrane of the cell.

Integrins
Cell surface receptor that connects to fibronectin, which
attaches to the ECM
Span the membrane and bind on their cytoplasmic side to
associated proteins attached to microfilaments of the
cytoskeleton.
Transmits changes between the ECM and the
cytoskeleton it integrates changes occurring outside and
inside the cell.

The dierences between the various types of extracellular

matrix result from varia?ons on this general theme.

Tendons contain a high propor?on of brous proteins,
Car:lage contains a high concentra?on of polysaccharides
that form a rm compression-resistant gel.

In bone, the extracellular matrix is hardened by deposi?on
of calcium phosphate crystals.

The sheetlike structure of basal laminae also results from
the u?liza?on of matrix components that dier from those
found in connec?ve ?ssues.

Extracellular matrix (ECM)

Surrounds cell
Provides mechanical support
Controls the flow of nutrients
and signals to the cells
Consists of
Fibrous: collagen,
elastin, fibronectin, laminin
Non-fibrous: Proteoglycans
and polysaccharides

04/19/10

http://kentsimmons.uwinnipeg.ca/cm1504

Cell proliferation

Cell survival

Cell migration

Cell growth

ECM

Cell death

Cell shape

Apoptosis

Cell differentiation

ECM plays role in almost each event of cell

27

The functions of ECM:

1. Plays important role to the survival, growth, and death of cells. Eukaryotic cells
must attach to ECM for their growth excepting blood cells, that we call as
anchorage dependence. For example, epithelial cells will turn to apoptosis if they
are separated from ECM. Different ECM will give cell different effects. The
proliferation of fibroblast will be quick up on a fibronectin matrix, and slow
down on a laminin matrix, but the response of epithelial cells to the matrix is just
opposite.
2. Controlls the shape of cell. Cells will be spherical if they grow with ECM
separately. A cell can present a different shape if it grow on a different ECM. The
mechanism of this regulation is mediated by the receptors on ECM that regulates
the cytoskeleton.
3Regulates the differentiation by the interaction between cell and special component
of ECM. For example, myoblast (sarcoblast) can keep its original shape on
fibronectin, but it will stop its proliferation to differentiate and fuse to myotube.
4Mediates cell migration. ECM can regulate the speed and direction of the migration.
Laminin can enhance the migration of tumor cells, and the migration of other
cells is dependent on ECM too. This dependence is very important during the
embryo development and wounds healing.
So, ECM mediate almost every event in cell and life story.
28


In bone, for example, a mineralized
extracellular matrix is designed to provide
support and resist compression.

In some cases, the matrix simply lls up the
space between dierent types of ?ssue,
ensuring that they are kept separate and that
their func?ons are not disturbed.

The skin has an extensive extracellular matrix

that keeps it elas?c and strong. The skin's matrix
also plays an important role in the healing
process, as do such structures elsewhere in the
body.

It can also help to regulate communica?on
between cells and the produc?on of certain
substances in the body.

In addi?on, it provides a framework for cell
adhesion, encouraging growth and stable
healing.

Depending on the type of extracellular matrix is

involved, specic cells may be required to build it.

Fibroblasts, for example, secrete the matrix that
creates brous connec:ve :ssue, while
osteoblasts make new bone.

When these cells are disrupted in some way, it can
cause serious problems, as the body constantly
reabsorbs the substances it makes even as it
produces more;

if no more is being produced, or the matrix is being
overproduced, it can cause health condi?ons.

Bones, muscles, and tendons all have extensive

extracellular matrices that allow them to perform
a variety of func?ons in the body.

Tendons and ligaments have special proteins that
allow them to be stretched and contracted so that
the body can be moved

Bone is made primarily from collagen and mineral
deposits, crea?ng a very solid, secure structure.

Summary: interactions cell-ECM

Major EC structural protein:

What are the major proteins of the ECM?

Collagens, Proteoglycans, Elastin, Fibronectin, Laminin, Tenascin.

Fig. 6-32

Tight Junctions
prevent extracellular
fluid from leaking
across epithelial
cells.

Tight junc:on

Tight junc:ons prevent
uid from moving
across a layer of cells

0.5 m

Tight junc:on

fasten cells together.

Intermediate
laments

Desmosome

Desmosome

Gap
junc:ons

Space
between
cells

Plasma membranes
of adjacent cells

Extracellular
matrix

1 m

Gap junc:on

0.1 m

allow ions, sugars,

amino acids, and
other things cells
need to pass from
cell to cell.

 Tight junc?ons can bind cells together into

leakproof sheets
Anchoring
junctions link
animal cells
Gap junctions
allow substances
to flow from cell
to cell

Through plasmodesmata, water and small solutes (and

some?mes proteins and RNA) can pass from cell to cell

Fig. 6-31

Cell walls

Interior
of cell

Interior
of cell

0.5 m

Plasmodesmata

Plasma membranes

Cancer
When cancers aback the body, one of the
things they assault rst is the extracellular
matrix in the region where they grow.

Cancers secrete certain enzymes that digest
the structure, providing a direct link with the
?ssue beneath it and allowing the cancer to
metastasize as it breaks up and distributes
cells to new regions.

Without these enzymes, the cancer would not
be able to penetrate the vulnerable ?ssue of
the body.

Of the deaths abributed to cancer, 90% are due to metastasis, and treatments that
prevent or cure metastasis remain elusive. Emerging data indicate that hypoxia and
the extracellular matrix (ECM) might have crucial roles in metastasis. During tumour
evolu?on, changes in the composi?on and the overall content of the ECM reect both
its biophysical and biological proper?es and these strongly inuence tumour and
stromal cell proper?es, such as prolifera?on and mo?lity.

Metastasis

Figure 14.17b The Biology of Cancer ( Garland Science 2007)

Metastasis
Definition : the spread of a tumor within the body
Metastatic cells factor :
1.less adhesive
2. Can penetrate numerous barriers
3.can invade normal
tissues

Where do they go?

Metasta:c tropism

Figure 14.42 The Biology of Cancer ( Garland Science 2007)

Hemostasis: a process which causes bleeding to stop

The prolifera?on phase is characterized by

angiogenesis,neovasculariza?on , collagen
deposi?on, granula?on ?ssue forma?on (new
connec?ve ?ssue and ?ny blood vessels),
epithelializa?on, and wound contrac?on.
The matura?on phase: when the levels of
collagen produc?on and degrada?on equalize.

Pathologic complications, 2
Excessive formation of repair components:

Excessive granulation tissue

Desmoid tumor (aggressive fibromatosis)
Best viewed as low grade neoplasm with stubborn tendency
for recurrences