Multi-channel kinetics of fibrin network self-assembly

Abstract

Fibrin networks are responsible for blood clotting and are widely used in tissue engineering and numerous biomedical applications. We developed a coarse-grained kinetic theory of self-assembly of fibrin networks from homogeneous solutions of fibrinogen and thrombin. Thrombin converts fibrinogen into fibrin monomers. The polymerization of these monomers results in the formation of intermediate products, protofibrils. Fibrin fibers form as a result of the diffusion-controlled aggregation of protofibrils. We considered two competing channels of fiber growth: the attachment of protofibrils to the ends of fibers, leading to fiber elongation, and lateral aggregation, increasing the diameter of fibers. The presented diagram of network self-assembly shows two main regimes. In a single-stage, thrombin-controlled regime, the protofibrils are immediately deposited onto network fibers. In a two-stage, kinetically controlled regime, network fibers form from a pre-existing solution of protofibrils. We determined the analytical dependencies of the gel formation rate and network structure parameters on fibrinogen and thrombin concentrations and reaction rates. These results are consistent with the experimental data obtained under physiological conditions, as well as at various ionic strengths and pH levels.