Extracellular Matrix

By Levi Clancy for Student Reader on
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The extracellular matrix is critical for many functions, including cell-cell signaling and tissue stability.

The ECM fulfills a variety of functions. It binds cells together and provides the stability for a tissue to withstand stretching and compression forces. It provides the structure that supports and guides migrating cells. Also, it contains molecules which, by binding to membrane molecules such as integrins, induce structural and biochemical changes in the cells to which they bind, thereby changing the developmental fate of these cells.

Integrin Receptors

The extracellular matrix (ECM) and basement membrane contain large amounts of collagen, a versatile signaling molecule which binds integrin receptors.

When bound to their ligand, integrins induce changes to gene expression, rate of proliferation and the cytoskeleton. Integrin-/- mutants lack epithelio-mesenchymal interactions.

Migration

The function of collagen and other ECM components in migration is very complex

Depending on their concentration and localization on the membrane, adhesion molecules at the same time antagonize or promote migration. The same can be said for collagen fibrils. To generate a force pulling a cell in one direction, the binding of integrin to collagen of the surrounding ECM is required.

On the other hand, the dense “underbrush” of collagen fibrils in the basal lamina is a hindrance to migration, so that migrating cells may need to secrete enzymes (collagenases) that degrade collagen. Interestingly, collagens can stimulate collagenase secretion.

Epidermal cells at wound margins come in contact with collagen I.

Via integrin binding, collagen I induces the secretion of a collagenase that will degrade collagen and thereby facilitate the ability of the epidermal cells to cover the wound during the healing process.

Cell-Cell Signaling

ECM molecules can also bind to secreted signaling molecules such as FGF, TGF-beta, and BMPs.

By this activity, ECM molecultes can sequester a pool of these signaling molecules that can be slowly released and thereby exert a sustained effect on receptors. Binding of a signaling molecule to ECM is in some cases required for the activation of specific receptors. An example is FGF that can activate its receptor only while it is linked to ECM. In this manner, some ECM molecules can be viewed as “cosignaling” molecules that in conjunction with the signals may excert complex effects on cell behavior.

Development

The most important cell type distinction in embryos is that between epithelial and mesenchymal cells.

These two cell types form quite different extracellular matrices. Epithelial cells secrete ECM proteins predominantly at their basal membrane where they assemble into a flat sheet underlying the basal surface of the epithelium. This type of ECM is called basement membrane. Mesenchymal cells secrete ECM proteins all around their membrane. In this manner, mesenchymal cells become embedded in an ECM.

All cells of a developing organism secrete a mixture of proteins into the extracellular space which form the extracellular matrix (ECM).

The most abundant proteins in the ECM are collagens, proteoglycans, and glycoproteins. These proteins are elongated, fibrillar molecules that become organized in a complex three-dimensional mesh, not too different from the cytoskeleton found inside cells. The biochemical composition of the ECM and the pattern in which ECM fibers are arranged depends largely on the type of cell that forms the ECM.