THE BEHAVIOR OF COLLAGEN UNITS AS A MODEL IN MORPHOGENESIS

Among the most intriguing problems in biology is that which deals with the formation, on supmmolecular and tissue levels, of morphologically specific and repeatedly reproduced structures. On the macromolecular level, the controlled formation of highly organized fibrils, crystallites, and two dimensional sheets from solutions of collagen molecules furnishes an interesting model system for the study of such phenomena. The reconstitution of collagen fibrils by increasing the pH or ionic strength of acid solutions of this protein is an old and familiar story (8, 31, 35). An exciting development was the revelation by electron microscopy that the reconstituted fibrils had the same precisely ordered morphology as did the native fibrils, namely the repeating axial period of about 640 A plus the detailed fine structure (1, 21, 38, 42, 51, 52). The two aspects of the problem which have engaged the attention of most investigators in this area are the characterization of the molecule and elucidation of the mechanism of in vitro fibrogenesis with the hope of relating it to the in vivo physiological process. Recent observations (16, 21, 27, 28, 48) on the production of radically different morphological forms of collagen by controlling conditions of pH and ionic strength, and by the addition of well characterized, non-collagenous substances, may bear pertinently on problems of morphogenesis in the organism. These may be summarized as follows:-1. An apparently homogeneous population of macromolecules may be precipitated from solution under the influence of physical chemical forces in the form of highly ordered structures, even when in the presence of a wrie ty of other high molecular weight substances. 2. The morphological characteristics of the precipitated structures may vary so radically as to appear completely unrelated to each other, depending on