Association of calcium and phosphate ions with collagen in the mineralization of vertebrate tissues.

Among the vertebrate species, collagen is the most abundant protein and is associated with mineralization of their skeleton and dentition in all tissues except enamel. In such tissues, bones, calcifying tendon, dentin, and cementum are comprised principally of type I collagen, which has been proposed as a template for apatite mineral formation. Recent considerations of the interaction between type I collagen and calcium and phosphate ions as the major constituents of apatite have suggested that collagen polypeptide stereochemistry underlies binding of these ions at sites within collagen hole and overlap regions and leads to nucleation of crystals. The concept is fundamental to understanding both normal and abnormal mineralization, and it is reviewed in this article. Given this background, avenues for additional research studies in vertebrate mineralization will also be described. The latter include, for instance, how mineralization events subsequent to nucleation, that is, crystal growth and development, occur and whether they, too, are directed by collagen stereochemical parameters; whether mineralization can be expected in all spaces between collagen molecules; whether the side chains of charged amino acid residues actually point toward and into the hole and overlap collagen spaces to provide putative binding sites for calcium and phosphate ions; and what phenomena may be responsible for mineralization beyond hole and overlap zones and into extracellular tissue regions between collagen structural units. These questions will be discussed to provide a broader understanding of collagen contributions to potential mechanisms of vertebrate mineralization.