A multiscale framework for modeling fibrin fiber networks: Theory development and validation

Abstract

Fibrin fibers and fibrin network, the key structural components of blood clots, are imperative for maintaining the functionality of blood clots in hemostasis and wound healing. Although extensive experimental investigations have lent valuable insights into the link between structure of fibrin network and the mechanical behavior of the blood clots, there is a lack of approaches to systematically quantify how the alterations in the microstructure of fibrin network dictate its mechanical responses to various external loadings. Such quantitative knowledge is essential for understanding the mechanism underlying thromboembolism, a pathological condition that could trigger life-threating events, such as pulmonary embolism. Herein, we present a multiscale framework for modeling a fibrin fiber network constructed by individual fibrin fibers. First, we develop a mechanical model for fibrin fibers using constitutive equations to capture both the tensile and bending behaviors of individual fibrin fibers. In particular, we propose an equation to describe the radial packing structure of protofibrils in the fibrin fiber cross-section, through which we can incorporate the microscopic variables, i.e., protofibril density, fiber radius, and the stiffnesses of αC-regions and fibrin protofibrils, into the derivation of a bending potential for the fibrin fiber model. With this derived bending potential, we show that the computed bending stiffness and persistence lengths of the fibrin fiber model are consistent with those reported in prior experimental studies. Next, we use the mechanical model of fibrin fibers to inform the parameters in a coarse-grained particle-based model for simulating fibrin network. Our simulation results show that the stress-strain relationships computed from fibrin network model when under tension, shear, and compression, align with experimental results, demonstrating the validity and capability of the proposed multiscale framework in modeling the mechanical responses of the fibrin network under various external loadings.