Investigation of Fibrin Fiber Deformation Theories: Insights from Phenomenological Modeling to Molecular Details

Abstract

The deformation mechanism of fibrin fibers has been a long-standing challenge to uncover due to the fiber’s complex structure and mechanical behaviors. In this paper, a phenomenological, bilinear, force-strain model is derived to accurately reproduce the fibrin fiber force-strain curve, then phenomenological model is then converted to a mechanistic model using empirical relationships developed from particle simulation data. The mechanistic model assumes that the initial linear fibrin fiber force-strain response is due to entropic extension of polypeptide chains, and the final linear response is due to enthalpic extension of protofibrils. When used to analyze experimental force-strain curves, the model predicts the number of protofibrils in the fiber’s cross-section, the entropic stiffness of αC-chains (polypeptide linkers between protofibrils), and the enthalpic stiffness of fibrin protofibrils. It predicts that the count of protofibrils through the cross-section for the analyzed fibrin fibers is between 207 and 421, the persistence length of αC-chains is 0.356nm, and the stiffness of protofibrils in a deforming fiber is 1.34nN/strain. This protofibril stiffness corresponds to half-staggered protofibrils of unfolded fibrin monomers. Our analysis supports the proposition that entropic extension of αC-chains could be responsible for fibrin fiber’s initial force-strain stiffness and suggests a structural change in fibrin protofibrils during fibrin fiber deformation. The results from the model are compared to those from five candidate deformation mechanisms reported in the literature. Our proposed model and data analysis offer insight into the fundamental understanding of structural and mechanical response of fibrin fibers in blood clots.

Keywords: fibrin fiber, Deformation mechanism, protofibrils, molecular dynamics, bilinear behavior