Extracellular matrix (ECM)

In the absence of cell wall many animal cells / tissues are surrounded by an ECM or ground
substance — an organized network of extracellular materials present beyond the immediate
vicinity of the plasma membrane. Most cells in multicellular organisms secrete proteins and
heteropolysaccharides into the extracellular space where they self assemble to form an organised
meshwork characteristic of the ECM. The ECM is more than inert nonspecific glue that holds
cells together; it often plays a key regulatory role in determining shape and activities of the cell.
One of the best studied extracellular matrices is the basement membrane (or basal lamina). It is a
continuous sheet that surrounds nerve fibers, muscles, and fat cells and underlies the basal
surface of epithelial tissues (epidermis of the skin), the lining of digestive and respiratory tracts
and endothelial lining of blood vessels. Basement membranes provide mechanical support for
attached cells, generate signals that dictate cell survival, serve as a substratum for cell migration
and act as a barrier to the passage of macromolecules. The ECM is most abundant in connective
tissues. The ECM is mainly composed of tough fibrous proteins embedded in a gel-like
polysaccharide ground substance - a design that is basically similar to that of plant cell walls. It
also has adhesion proteins that link components of the matrix to one another and to attached
cells.

Components of Extracellular matrix

1. Collagen: The major structural protein of ECM is Collagen. The collagens are a large
family of glycoproteins containing at least 27 different members which are produced by
fibroblasts, osteoblasts, chondrocytes and epithelial cells. Each collagen type is restricted
to particular locations within the body. The most abundant collagen is type I collagen. It
is one of the fibril forming collagens. Their polypeptide chains consist of approximately
1000 amino acids or 330 Gly-X-Pro or Gly-X-4-Hyp repeats. After secretion as soluble
precursors (procollagens) they are cleaved and assembled into collagen fibrils. All
members of the collagen family share at least two important structural features. First,
three separate polypeptides, called α-chains are supertwisted about each other. The
superhelical twisting is right handed in collagen. Second, many of the proline (and lysine)
residues of each α -chain are hydroxylated. The tight wrapping of α –chains in the triple
helix provides enormous tensile strength to collagen.
2. Elastin: Elastin is a key extracellular matrix (ECM) protein that provides resilience and
elasticity to tissues and organs. Elastin is roughly 1000 times more flexible than
collagens; thus, the main function of elastin is the elasticity of tissues. It is the dominant
protein in extensible tissues and is primarily present in the lungs, aorta, and skin.
Mutations in the elastin gene may lead to diseases such as Williams–Beuren syndrome,
cutis laxa, and supravalvular aortic stenosis (SVAS). The precursor of elastin
is tropoelastin. Tropoelastin is derived from fibroblasts, smooth muscle
cells, chondrocytes, or endothelial cells before it is processed to elastin by cleavage of
its signal peptide. The enzyme, lysyl oxidase, initiates cross-linking of the soluble
monomers into insoluble fibers. As a polymeric molecule, elastin has hydrophobic and
insoluble properties and can resist acid and alkali. In the presence of water, elastin exists
in the form of a rubbery extension. In addition, over 75% of the sequence of elastin
consists of just four non-polar amino acids, namely, glycine, valine, alanine, and proline.
Elastic fiber networks play an essential role in maintaining normal physiological
functions, conferring elasticity, and recoiling to tissues and organs.
3. Fibronectin (FN): Fibronectin is a critically important ECM protein that mediates
cell:ECM interaction during fundamental events such as development, wound healing,
fibrosis, and tumor progression (Schwarzbauer and DeSimone, 2011). Fibronectin is
secreted as a soluble, covalently bound dimer of ~440 kD molecular weight. The single
FN gene is highly conserved and produces at least 20 isoforms by alternative splicing
in humans. The most notable isoforms are cellular and plasma FN. The production of
plasma FN occurs in the liver, while cellular FN is produced locally by different cell
 types. The plasma form of FN circulates in the blood, and upon tissue injury, is
incorporated into fibrin clots to exert effects on platelet function and to mediate
hemostasis. Cellular FN is then synthesized and assembled by cells as they migrate into
the clot to reconstitute damaged tissue.Mutations in the FN gene may lead to variants of
FN glomerulopathy and spondylometaphyseal dysplasia. FN is a multi-domain
glycoprotein composed of three repeating units: 12 Type I, 2 Type II, and 15–17 Type III
domains and 1 variable region. One of the unique features of fibronectin is its ability to
specifically bind a large number of molecules including other components of the
extracellular matrix, signaling molecules, and cell adhesion molecules.

4. Laminin: Laminin, a glycoprotein localized specifically in basement membranes, is a

potent regulator of epithelial cell behavior. Numerous studies indicate that laminin has
diverse biological activities which include stimulating adhesion, migration, growth, and
differentiation of various cell. Also, laminin is known to increase metastatic behavior of
tumor cells. Laminins are heterotrimers consisting of one α, one β, and one γ chain. The
chains are covalently linked by disulphide bonds. Laminin plays a crucial role in neural
development, where it acts as a guiding path along which certain axons extend to find
their eventual synaptic targets. One prominent example is the retinotectal pathway that
leads retinal ganglion cell axons from the eye to the brain. Another example of the role of
laminin in development is the guidance of primordial germ cells (PGC). These are cells
that eventually become the gametes, but need to migrate from the yolk sac, which is
outside the embryo proper, to the site of gonad formation.