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Abstract:
Essentials Fibrinogen circulates in human plasma as a complex mixture of heterogeneous molecular variants. We measured strain-stiffening of recombinantly produced fibrinogen upon clotting. Factor XIII and molecular heterogeneity alter clot elasticity at the protofibril and fiber level. This highlights the hitherto unknown role of molecular composition in fibrin clot mechanics.

Keywords:
blood coagulation, elasticity, fibrin, polymers, rheology, turbidimetry

Abstract:
Bundles of polymer filaments are responsible for the rich and unique mechanical behaviors of many biomaterials, including cells and extracellular matrices. In fibrin biopolymers, whose nonlinear elastic properties are crucial for normal blood clotting, protofibrils self-assemble and bundle to form networks of semiflexible fibers. Here we show that the extraordinary strain-stiffening response of fibrin networks is a direct reflection of the hierarchical architecture of the fibrin fibers. We measure the rheology of networks of unbundled protofibrils and find excellent agreement with an affine model of extensible wormlike polymers. By direct comparison with these data, we show that physiological fibrin networks composed of thick fibers can be modeled as networks of tight protofibril bundles. We demonstrate that the tightness of coupling between protofibrils in the fibers can be tuned by the degree of enzymatic intermolecular crosslinking by the coagulation factor XIII. Furthermore, at high stress, the protofibrils contribute independently to the network elasticity, which may reflect a decoupling of the tight bundle structure. The hierarchical architecture of fibrin fibers can thus account for the nonlinearity and enormous elastic resilience characteristic of blood clots.