20 MACROMOLECULAR COMPLEXES 



apatite from solutions in metastable equilibrium with respect to 

 calcium and phosphate ions. There is reason to believe, also, that 

 the knowledge thus gained of the TC macromolecule and of its poly- 

 merization properties may prove useful in the elucidation of con- 

 nective tissue abnormalities such as characterize certain of the 

 rheumatoid diseases, atherosclerosis, and aging processes. 



The Tropocollagen Macromolecule 



The existence of a discrete type of collagen monomer extractable 

 from a variety of connective tissues under appropriate conditions 

 has been amply confirmed b)' a variety of techniques. Since both 

 small-angle x-ray diffraction (Bear, 1952) and electron microscope 

 studies on native fibrous collagen indicated a highly ordered band 

 structure with a fundamental repeat of about 640 A, it was assumed 

 bv many that the monomer must have a length of this dimension. 

 The first indication that this was not the case came with the ob- 

 serxation that soluble collagen could be reconstituted into "long- 

 spacing forms," which exhibited axial periods of several times the 

 value characteristic of native fibrils (for summaries, see Schmitt 

 et al, 1955; Schmitt, 1959; Hodge, 1959b). More recent measure- 

 ments (Hodge and Schmitt, 1960) show very sharp distributions 

 around length values of about 2800 A for these long-spacing forms, 

 corresponding to four times the native period, and comparably 

 sharp distributions for native-type fibrils. This value is in good 

 agreement with the results of Boedtker and Doty (1956), who 

 found by physicochemical methods that the macromolecules of 

 soluble collagen are highly asymmetric stiff rods with dimensions 

 of about 14 A X 2900 A, and with those of Hall and Doty (1958), 

 who utilized an improved shadow-casting technique for direct 

 visualization of macromolecules in the electron microscope. 



The large-angle x-ray diffraction pattern of collagen is one of its 

 most striking characteristics and has been interpreted ( see Rich and 

 Crick, 1958) as indicating the presence, over large regions of the 

 fibrous structure, of a three-stranded helical configuration of poly- 

 peptide chains which involves the sequence glycine-proline-hy- 

 droxyproline well known from degradative experiments, the whole 

 structure being stabilized by hydrogen bonding. The three-stranded 

 model is also supported indirectly by the observe ions of Doty and 

 Nishihara (1958) on the denaturation of soluble collagen. On de- 



