ABSTRACT
The effect of molecular "aging" of fibrinogen stimulated by preincubation in solution on the fibrin three-dimensional architecture, its ability to crosslink fibrin-stabilizing factor, and the sensitivity of fibrin gel to plasmin hydrolysis have been studied. The method of elastic light scattering was used to demonstrate that fibrin generated from "defective" fibrinogen had a coarser structure with a higher mean mass-length ratio of polymeric fibers compared to native fibrinogen (2.24 x 10(9) and 1.46 x 10(9) g/(mol x cm), respectively). Crosslinking had no effect on the architecture of both control and experimental fibrin samples. Spectrophotometric and electrophoretic analysis has shown a higher sensitivity of coarse fibrin gels to plasmin. A close correlation between spontaneous local conformational reconstructions in fibrinogen molecule and its functional activity is concluded.
Subject(s)
Fibrin/chemistry , Fibrinogen/chemistry , Fibrinolysin/chemistry , Animals , Cattle , Gels/chemistry , Protein Structure, Quaternary , Structure-Activity Relationship , Time FactorsABSTRACT
We studied the influence of the end products of plasmin-mediated hydrolysis of fibrinogen and nonstabilized fibrin (EF and Ef fragments) on covalent cross-linking of fibrinogen molecules catalyzed by a fibrin-stabilizing factor (factor XIIIa). The data on elastic and dynamic light scattering reveal no difference in the spatial structure of covalently linked fibrinogen molecules in the presence of the hydrolysis end products EF and Ef. In contrast to the inactive fragment EF, fragment Ef significantly accelerates the enzymatic reaction. This is also confirmed by electrophoresis of the reduced samples indicating a relatively fast accumulation of gamma-dimers and A alpha-polymers as compared to the control samples. Possible molecular mechanisms of this effect are discussed.
