Extracellular matrix

Collagens are the most abundant ECM proteins (classically estimated at about a quarter to a third of total body protein; recent direct measurements suggest somewhat less). There are 28 types, each a triple helix of three α-chains with the repeating sequence Gly–X–Y (X often proline, Y often hydroxyproline); glycine, the smallest amino acid, fits in the centre of the helix. Key types: I — thick fibres of bone, skin, tendon, ligaments, dentin, cornea, sclera and scar (≈90 % of body collagen); II — fine fibrils of hyaline and elastic cartilage, nucleus pulposus and vitreous body; III — reticular fibres of lymphoid organs, marrow, blood vessels, skin and granulation tissue; IV — non-fibrillar network of basal laminae; VII — anchoring fibrils under stratified epithelia. Elastic fibres (elastin on a fibrillin scaffold) give recoil.

Collagen synthesis (fibroblasts, osteoblasts, chondroblasts): (1) translation of pre-pro-α chains into the RER; (2) hydroxylation of proline and lysine (prolyl/lysyl hydroxylases need vitamin C); (3) glycosylation of hydroxylysine; (4) assembly of the procollagen triple helix (disulfide bonds in the C-propeptides); (5) Golgi packaging and exocytosis; (6) outside the cell, procollagen peptidases remove the propeptides → tropocollagen; (7) self-assembly into staggered fibrils (64–67 nm banding) and covalent cross-linking by copper-dependent lysyl oxidase.

Ground substance is a hydrated gel. Glycosaminoglycans (GAGs) are long unbranched polysaccharides of repeating disaccharides, highly negatively charged (carboxyl and sulfate groups), so they attract Na⁺ and water and resist compression. Hyaluronan (hyaluronic acid) is huge, non-sulfated and not attached to protein; the others — chondroitin sulfate, keratan sulfate, dermatan sulfate, heparan sulfate — are bound to core proteins as proteoglycans (e.g. aggrecan in cartilage, which attaches by link protein to hyaluronan to form giant aggregates; perlecan in basal laminae; syndecans on cell surfaces). Multi-adhesive glycoproteins — fibronectin and laminin — link cells (via integrins) to collagen and proteoglycans. Matrix is continuously remodelled by matrix metalloproteinases (MMPs, e.g. collagenases), held in check by TIMPs.