Abstract

Collagen is the major protein of animal bodies from simple sponges to Homo sapiens and exists in various forms from skin, tendon and bone to cornea and basement membrane of the capillaries. This biological variation can now be accounted for on the basis of a whole family of genetically distinct collagens. Over the past two decades 19 different collagens have been identified, although the major types are the fibrous types I, II and III and the non-fibrous type IV of basement membrane. They all possess the basic triple helix based on multiple repeats of the simple tri-peptide Gly—X—Y, but this varies in length and forms different supramolecular aggregates to achieve optimum function for particular tissues. The major function of collagen is to provide shape and mechanical strength and the latter is achieved by intermolecular crosslinking of the collagen molecules in the supramolecular aggregate. The monomeric molectiles in the aggregates are stabilised by two different pathways. Initially cross-linking occurs through an enzymic mechanism involving oxidation of specific lysine and hydroxylysine residues providing divalent crosslinking which subsequently matures to multivalent cross-links. As the rate of turnover decreases a non enzymic pathway takes over, which is mediated through the adventitious accretion of glucose. Collagen therefore, unlike other proteins shows considerable changes with age which in turn affect its physical properties. These changes must be taken into account when preparing collagen based products.

All the amino acid side chains project radially from the rod-like triple helix and the quarter-staggered array of the molecules allows highly specific intermolecular cross-linking either naturally, or artificially with bifunctional reagents. Reactions with basic or acid groups can therefore be carefully controlled and in some cases their location predicted. Synthetic cross-links bind the molecules closer together and increase intermolecular interactions, thus increasing the shrinkage temperature and resistance to enzymic degradation.

The turnover of collagen is generally slow but in fact can vary from 2/3 days for periodontal ligament to several years for skin and tendon. Mature collagen fibres are highly resistant to enzymes and degradation is achieved by specific collagenase that can cleave the triple helix at one particular point. The shorter helical fragments can then unravel and denature to gelatin when other metalloproteinases (MMPs) degrade it to amino acids. A family of 14 metalloproteinases have been identified along with some specific tissue inhibitors (TIMPS).

The sharp denaturation temperature of collagen attests to the almost crystalline character of the triple helix and the variation in shrinkage temperature between species is primarily due to the number of hydroxyproline based water hydrogen bridges. The presence of a hydroxyproline deficient thermally labile domain near the carboxy terminus of the molecule initiates the melting process allowing the triple helix to unzip along its length.

Recent studies have demonstrated that collagen is not an inert structural material but interacts with other molecules to control the development of collagenous tissues. Despite the ancient lineage of this ubiquitous protein, collagen is still revealing exciting new scientific features.