Albumin indirectly modulates fibrin and protofibrin ultrastructure.

Abstract

Albumin modulation of fibrin and protofibrin coagulation parameters was studied. Cation-depleted, fatty acid free, human and bovine albumins decrease fibrin clot turbidity in a concentration-dependent manner. Albumin also inhibits the formation of protofibrin gels, induced by addition of 25 microM Zn(II) to protofibrils, though it does not bind to (proto)fibrin. In order to verify that competition for cations underlies the influence of albumin, fibrinogen was dialyzed against cation-depleted albumin. Elemental analysis indicates a redistribution of Zn(II) from the fibrinogen to the albumin compartment, and the resultant fibrin clots are less turbid. Apparently, cation-depleted albumin acts as a competitor for divalent cations. The ability of albumin to compete for available Zn(II) was also expressed in gels formed by pH-jump experiments, in which fibrin monomer, maintained soluble at pH 4.9, is induced to change phase by addition of NaOH to pH 7.4. While turbidimetric evidence indicates that individual fibrin fibers simply become thinner with albumin, scanning electron micrographs (SEM) reveal a more complex effect on ultrastructure. Though albumin does not bind to the gels, fibrin gels produced with albumin show major changes in fiber ultrastructure, particularly evident in gels formed in the presence of Zn(II). These structural modifications are discussed within the context of the "excluded volume" effect, in which "crowding" by albumin alters (proto)fibrin reactivity and ultrastructure.