A molecular model of plasmic degradation of crosslinked fibrin.

Based on structural studies of both degrading insoluble crosslinked fibrin and of soluble derivatives, we have developed a model to explain the principal structural and physical features of plasmic degradation for crosslinked fibrin in vitro from the completely intact matrix to terminally degraded soluble derivatives. Plasmic digestion is viewed as a continuous process of proteolytic attack on accessible, enzyme-susceptible sites; but the process is separated into four phases based on solubility characteristics of the degrading fibrin matrix and on the structures of the soluble derivatives. The critical event of solubilization occurs only as the result of coincident cleavages at complementary sites in the basic two-stranded half-staggered overlap fibrin structure, resulting in the release of two-stranded complexes held together by noncovalent forces. The four smallest complexes which are released into solution have structures corresponding to DD/E, DY/YD, YY/DXD, and YXD/DXY. The protein initially solubilized has a constant composition with a predominance of large derivatives which are composed of at least on fragment from each of the two strands of the protofibril. Following their release into solution the larger complexes are converted in vitro to smaller ones by the continued action of plasmin, so that the complex found following prolonged digestion is DD/E. It is proposed that this newly defined group of complexes [11] represents the major form of circulating plasmic derivatives of crosslinked fibrin.