MACROMOLECULAR AGGREGATES IN CALCIFICATION 55 



been presented (Glimcher et al., 1957; Glimcher 1958; Glimcher, 

 1959; Glimcher et al, 1960a, 1960b) and therefore need only be 

 summarized here. 



The basis of the hypothesis rests on an understanding of the 

 phvsicochemical phenomena involved in phase transitions, of which 

 crvstallization is just one specific case (Turnbull, 1956; Glimcher, 

 1959). A common example of a phase transition is the formation of 

 ice cr\'stals from liquid water or from supersaturated water vapor. 

 The use of Agl crystals in "seeding" supersaturated water vapor to 

 initiate ice crystal formation is well known. The formation of a new 

 phase (i.e., ice from supersaturated vapor) by the use or introduc- 

 tion of such a seeding material is called heterogeneous nucleation. 

 Two important points should be noted : ( 1 ) The water vapor or 

 liquid water must be supersaturated, that is, in metastable equilib- 

 rium; systems in metastable equilibrium may remain stable indefi- 

 nitely yet still retain the ability to form a new phase under the proper 

 conditions, "seeding," for example. ( 2 ) The "seed" crystal must have 

 an atomic lattice structure similar to that of the crystal being nu- 

 cleated (Turnbull, 1950a, 1950b, 1952; Turnbull and Vonnegut, 

 1952 ) ; in the case of Agl and ice, for example, there is a remarkably 

 close fit between their lattice parameters. 



Examination of the biological conditions as they relate to calcifi- 

 cation of bone, cartilage, and tooth reveals some interesting correla- 

 tions. The extracellular fluids of many vertebrates have been shown 

 to be in metastable equilibrium with respect to the formation of 

 apatite crystals (Neuman, 1950; Strates et al, 1957; Strates and 

 Neuman, 1958; Glimcher, 1959). Furthermore, the major organic 

 component of bone, of cartilage, and of the dentin and cementum 

 of tooth is the fibrous protein, collagen. This complex macromol- 

 ecule, which is thought to be composed of three polypeptide chains 

 in a coiled-coil configuration (Rich and Grick, 1955, 1958), is so 

 structurally regular that it gives rise to a characteristic x-ray diffrac- 

 tion pattern and therefore for our purpose may be considered 

 "crystalline" (Fig. 1). In addition, the native collagen fibril, which 

 is composed of such macromolecules aggregated both linearly and 

 longitudinally in a highly specific and characteristic fashion, is there- 

 fore also a well-ordered structure and may also be considered "crys- 

 talline" (Fig. 2). When to such data is added the observation of 

 the intimate association between the apatite crystals and collagen 

 (the inorganic apatite crystals in bone are located primarily within 



