DIFFERENTIATION AND PROTEIN SYNTHESIS 127 



have been extensively studied and draw what inferences we can about the 

 formation of keratin. 



Collagen. By far the best understood case is that of collagen. As was 

 well demonstrated by Nageotte (1927), collagen is an admirable protein for 

 research on fibrogenesis since its solution in weak acids can very readily be 

 made to reform fibres. Today largely owing to the work of Schmitt and 

 Bear and their associates (1955 and 1960) and of Randall and Jackson 

 (1956) (Randall and Robinson, 1953) it has become the prototype model 

 for studies of morphogenesis at the macromolecular level. Not only may 

 it be readily dissolved and regenerated in fibrous form; it also yields, 

 when conditions are changed, a remarkable variety of fibrous fabrics some 

 of which are not found in nature (Hodge, 1960). The precursor is synthe- 

 sized by fibroblasts and secreted as a soluble molecule into the inter- 

 cellular space where it proceeds to form fibrils and fabrics which are 

 exquisitely adapted to the demands of the mechanical forces operative at 

 that point (see Plate 23B). 



Soluble collagen, or tropocollagen, has been shown by light scattering 

 (Boedtker and Doty, 1956; Cohen, 1955) to have a long (3000 A) thin 

 (13-6 A) molecule composed of three helically coiled chains, strongly- 

 H-bonded, of molecular weight about 345,000 in Stainsby, 1958). This 

 long molecule is able to aggregate, principally by lateral adhesion, to 

 yield a variety of structures in addition to that normally found in native 

 collagen fibres and each is recognized electron-microscopically by its 

 banded structure. For recent summaries, see Bear (1952), Robinson 

 (1953), Randell et al. (1953) and Hodge (I960). 



The possible arrangements of both intact and partially fragmented 

 molecules have been very fully worked out and are shown diagrammatically 

 in Fig. 55. It is characteristic of the collagen type of lateral aggregation of 

 long thin precursors that there should be large well-marked longitudinal 

 repeat spacings detectable by X-rays or electron microscopy, and an 

 absence of side spacings larger than that corresponding to the molecular 

 diameter. The existence, in the X-ray patterns (see Chapter 5) of well- 

 formed examples of fibrous keratin, of strong long-spacings on the 

 equator, i.e. side spacings (Tables 9 and 10, p. 167), and the absence of the 

 lower orders of the main longitudinal repeat pattern, suggests that the 

 collagen model is not immediately applicable to keratin. Electron- 

 microscopically, the keratin protofibrils are seen to be thicker (60 A) than 

 the collagen unit, and of indefinite length (at least 2000 A long), and no 

 marked longitudinal spacing is visible electron-microscopically, although 

 long spacings expressible as orders of a major spacing of 198 A (hair) and 

 98 A (feather) are found in X-ray diffraction patterns (Chapter 5). 



The aggregation of filaments to form muscles seems in principle to be 

 very like that involved in collagen formation (Hodge, 1959 and 1960). 



