STUDIES ON THE FORMATION OF COLLAGEN III. 'IkME-DEI'ENDENT SOLUBILITY CHANGES OF COLLAGEN IN VITRO*

Extraction of collagen from fresh connective tissue in various aqueous media and the influence on extractibility of factors such as age, growth rate, and vitamin C deficiency have been the subject of a number of descriptive studies. Little is known concerning the mechanism of the observed solubility changes. The amount of collagen extracted from skin in acid buffers such as citrate, pH 3.5, is diminished with age (2, 3) and in scurvy (2). The amount of collagen extracted in cold neutral salt solutions is a direct function of growth rate and is considerably reduced with loss of body weight (4). Rapid growth, which increases the amount of this collagen fraction in the skins of normal guinea pigs, will not do so in scorbutic animals (5). I t has been postulated (6-9) that the collagen fraction extracted from skin in cold neutral or mildly alkaline salt solutions is newly synthesized and is spontaneously aggregated to form cross-striated fibrils in the extracellular ground substance. A plausible in vitro model of fibrogenesis is the observed precipitation of fibrils (characteristic of the native tissue) as a gel, which occurs on warming cold neutral salt solutions of collagen (7, 8, 10-12). The present study represents a further exploration of the behavior of this model system and offers a possible explanation for the growth and age related changes in solubility of fresh tissue collagen in neutral and acidic media.