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Cellular biomechanics-ECM

Cellmatrix interactions
Cellmatrix interactions
To function properly, cells must stay attached to their
substrates and to their neighbours. The exceptions are
circulating cells, such as formed elements in the blood

In some cases: vascular endothelial cell in a large artery it


lives on a continuously deforming substrate to which it must
adhere, while maintaining close contact with its neighboring
endothelial cells

Furthermore, it must be able to detach locally from its


substrate, for example to crawl to cover a denuded region of
the artery wall following injury or to allow a circulating
macrophage to enter the artery wall
Cellmatrix interactions
In addition, the cell senses some aspects of its
biomechanical environment through
deformations of its substrate
interaction with its substrate influences
cytoskeletal structure,
phagocytosis (ingestion of foreign material),
and
signal transduction.
ECM
There are two kinds of attachment that cells make: to
neighbouring cells and to their substrates

Extracellular materials that form the cells substrate

This extracellular material is a complex mixture of


biopolymers that is collectively known as the
extracellular matrix (ECM).

Immediately adjacent to some cells (e.g., endothelial


cells, epithelial cells, muscle cells, fat cells, Schwann
cells of the nervous system), there is a specialized layer
known as the basal lamina, or basement membrane,
which is a specialized region of the ECM.
ECM components
In general, the ECM is very complex and
consists of a large number of highly
specialized macromolecules.
Some of the important components are:
1. Collagens
2. Elastin
3. Proteoglycans
4. Hyaluronan
5. Adhesion proteins
6. Integrins
Collagens
Collagen is a fibrous protein that imparts
structure and rigidity to tissue.
It occurs in many different types, and is the most
abundant protein in higher vertebrates; collagen
makes up one third or more of total body protein
collagen type I: forms large structural bundles
that are present in tendons, ligaments, and other
tissues subject to significant mechanical loading
It has high tensile strength 1 109 Pa
Collagen
collagen type IV: forms X-shaped complexes
that associate together to create a highly
interconnected fibrous network; is abundant in
basement membrane

collagen type VI: widely distributed throughout


the ECM, this collagen type seems to play an
intermediate role between the interstitial
collagens (types IIII) and cells, helping cells to
form attachments to the surrounding matrix
Elastin
This fibrous elastic protein acts to impart elasticity
and resilience to tissue

It is much more compliant than collagen (Youngs


modulus 3 104 Pa) and is present in significant
amounts in the walls of large arteries, lungs and skin
Proteoglycans
Proteoglycan is a generic term denoting a protein that has one or
more glycosaminoglycan (GAG) side chains.

The physicochemical properties of the proteoglycans are in large


part determined by the GAGs, which are themselves large
biopolymers made up of negatively charged carbohydrate repeat
units.

The GAGs are avidly hydrophilic and will imbibe and retain very
large volumes of water Common proteoglycans are
aggrecan (found in large amounts in cartilage)
heparin sulfate (found in basal lamina)
chondroitin sulfate,an important structural component of
cartilage and provides much of its resistance to compression
Hyaluronan
Hyaluronan (also called hyaluronate and hyaluronic
acid) is an extracellular GAG that is unusual in not
being covalently linked to a protein, although it
associates non-covalently with proteins in ECM

Its large size and strong negative charge means that


it is very effective at taking up water and keeping
tissue hydrated

Nonsulfated glycosaminoglycan distributed widely


throughout connective, epithelial, and neural tissues.
Adhesion proteins
Laminins and fibronectin are adhesion proteins

Laminin: there are 11 known isoforms of laminin, all


of which are cross shaped proteins that are abundant
in basal lamina and bind collagen type IV and other
matrix molecules; they are key components of the
basement membrane
Fibronectin: this large protein has binding domains
for collagen, cell-surface binding molecules
(integrins) and heparin sulfate; It is the all-purpose
glue of the ECM
A highly schematic diagram
showing some of the major
components of the
extracellular matrix, with a
flow pathway from
a vascular capillary (upper
portion of figure) to a
lymphatic capillary (lower
portion of figure).
1, an endothelial cell in a
capillary wall; 2, capillary
endothelial basement
membrane; 3, interstitial
matrix; 4, interstitial cell;
5, lymphatic capillary
endothelial cell;
6, lymphatic fluid; 7, elastic
fiber; 8, plasma proteins in
When these components are put together, a lymphatic fluid.
composite structure results
scaffolding
In this composite material, collagen and elastin act
together to provide mechanical integrity and tissue
structure, and to provide mechanical scaffolding for
the resident cells

While hyaluronan and the proteoglycans fill the empty


spaces and hold water in the tissue.

The role of the bound water in the tissue is crucial,


since this provides the pathway whereby nutrients and
other species are transported to and from the cells.
The entire structure can be thought of as a biological
sponge loaded with water
Integrins
Cells express transmembrane proteins called integrins
that are responsible for binding to specific components in
the matrix and attaching the cell to its substrate.

The integrins are heterodimers (formed by two dissimilar


subunits, an chain and a chain) that have an
extracellular binding domain, a transmembrane domain,
and a cytosolic domain.

There are at least 22 different integrins in mammals,


each of which specifically recognizes binding domains on
collagen, laminin, fibronectin, and/or other matrix
proteins
Focal adhesion complex-FAC
The cytosolic domain of the integrin associates
with a large protein grouping called a focal
adhesion complex, complex set of proteins,
including vinculin, talin, tensin, and -actinin.
which in turn attaches to F-actin filaments.

In this way, the actin filaments of the


cytoskeleton are ultimately connected to the
fibrous matrix outside the cell