Early events in the plasmin digestion of fibrinogen and fibrin. Effects of plasmin on fibrin polymerization.

We have studied the effects of limited plasmic digestion of fibrinogen and fibrin on the physical properties of fibrin gels. After limited digestion the rigidity (elasticity) of the clot formed from degraded fibrinogen is 1% of the rigidity obtained from undegraded fibrinogen, whereas the decrease in clottability as a result of this limited digestion is only about 10%. When plasmin digests fibrin in gel form, the degradation process is significantly prolonged; the rigidity of the attacked gel increases and remains high (hyper-rigidity) for 2 to 4 h and then disappears relatively abruptly. Plasmin cleaves the (Y (or Aa) chain and releases the hydrophilic, COOH-terminal portion (M, = 44,000). Plasmin apparently has a high affinity for a site about one-third of the way from the NH, terminus of the LY chain of fibrin; plasmin also prefers fibrin to fibrinogen as a substrate in a system where both species are present in equal amounts. The high affinity for the first site of lysis causes the digestion of fibrin to be orderly, in the sense that in the first phase of digestion only (Y chains are split, and the rigidity of the gel does not fall. The low rigidity of a fibrin gel formed from fibrinogen digested briefly with plasmin has been reproduced in a fibrin gel prepared by first briefly digesting fibrin with plasmin, then dissolving this material in NaBr, and finally allowing the fibrin to gel again. Fibrin molecules lacking the COOH-terminal two-thirds of the (Y chain form an abnormal network of fibrin fibers of low rigidity, whereas the normal fibrin network does not lose its rigidity when these same peptides are removed. It is suggested that the hydrophilic COOH-terminal twothirds of the a! chain serves to maintain a fibrin polymerization site in the adjacent portion of the NH,-terminal part of this chain exposed on the surface of the fibrin molecule.