Structural origins of fibrin clot rheology

The origins of clot rheological behavior associated with network morphology and factor XIIIa-induced crosslinking were studied in fibrin clots. Networ k morphology was manipulated by varying the concentrations of fibrinogen, t hrombin, and calcium ion, and cross-linking was controlled by a synthetic, active-center inhibitor of FXIIIa. Quantitative measurements of network fea tures (fiber lengths, fiber diameters, and fiber and branching densities) w ere made by analyzing computerized three-dimensional models constructed fro m stereo pairs of scanning electron micrographs. Large fiber diameters and lengths were established only when branching was minimal, and increases in fiber length were generally associated with increases in fiber diameter. Ju nctions at which three fibers joined were the dominant branchpoint type. Vi scoelastic properties of the clots were measured with a rheometer and were correlated with structural features of the networks. At constant fibrinogen but varying thrombin and calcium concentrations, maximal rigidities were e stablished in samples (both cross-linked and noncross-linked) which display ed a balance between large fiber sizes and great branching. Clot rigidity w as also enhanced by increasing fiber and branchpoint densities at greater f ibrinogen concentrations. Network morphology is only minimally altered by t he FXIIIa-catalyzed cross-linking reaction, which seems to:augment clot rig idity most likely by the stiffening of existing fibers.