The extracellular matrix is a meshwork of proteins and carbohydrates that binds cells together or divides one tissue from another. The extracellular matrix is the product principally of connective tissue , one of the four fundamental tissue types, but may also be produced by other cell types, including those in epithelial tissues. In the connective tissue, matrix is secreted by connective tissue cells into the space surrounding them, where it serves to bind cells together. The extracellular matrix forms the basal lamina, a complex sheet of extracellular matrix molecules that separates different tissue types, such as binding the epithelial tissue of the outer layer of skin to the underlying dermis, which is connective tissue. Cartilage is a connective tissue type that is principally composed of matrix, with relatively few cells.
Collagens are the principal proteins of the extracellular matrix. They are structural proteins that provide tissues with strength and flexibility, and serve other essential roles as well. They are the most abundant proteins found in many vertebrates. There are at least nineteen collagen family members whose subunits, termed α chains, are encoded by at least twenty-five genes . The primary protein sequence of all collagen subunits contains repeating sequences of three amino acids , the first being glycine with the second and third being any amino acid residue (sometimes referred to as a GLY–X–Y motif).
Most, if not all, collagens assemble as trimers , with three subunits coming together to form a tightly coiled helix that confers rigidity on each collagen molecule. Assembly of the collagen trimer occurs in the cell by a self-assembly process, which is mediated by short amino acid sequences at both ends of each subunit, called propeptides. Some collagens, most notably collagen types I, II, III, and V, assemble into large, ropelike macrofibrils once they are secreted into the extracellular matrix. In these cases, the propeptides are cleaved off following secretion , permitting the trimeric molecules to undergo further self-assembly into fibrils. In the electron microscope each of these macrofibrils has a characteristic banded appearance and can be very large (up to 300 nanometers in diameter).
Type IV collagen, which is found in the basal lamina, does not assemble into a fibril since its subunits retain their propeptides following secretion from a cell. Its triple helix has a series of interruptions in the GLY–X–Y repeating motif, preventing the subunits from binding quite as tightly, and giving the molecule more flexibility. Type IV collagen forms a scaffold around which other basal lamina molecules assemble. In contrast to the fibril-forming collagens and type IV collagen, type XVII collagen is membrane-spanning protein. It is a component of a cell/matrix junction called the hemidesmosome.
The fibrillar collagens are also associated with a class of collagen molecules that themselves do not form fibrils but that appear to play an important role in organizing the highly ordered arrays of collagen fibrils that occur in some connective tissues. Examples of this collagen class include type IX and type XII collagen.
Collagens do not simply provide filler for tissues. Both fibrillar and basal lamina collagens interact with other extracellular matrix proteins and play important roles in regulating the activities of the cells with which they interact. Cells associate with collagen via cell surface receptors, and through such interactions collagens may have a profound impact on cell proliferation, migration, and differentiation. Fibers and meshworks of collagen molecules also act as a repository of growth factors and matrix-degrading enzymes . These are often present in inactive form and become activated in order for tissues to undergo remodeling, for example in development, during cyclical changes in the female reproductive system, and in pathological conditions such as cancer.
Alberts, Bruce, et al. Molecular Biology of the Cell, 4th ed. New York: Garland Publishing, 2000.