Development of a mesoscopic framework spanning nanoscale protofibril dynamics to macro-scale fibrin clot formation.

Abstract

Thrombi form a micro-scale fibrin network consisting of an interlinked structure of nanoscale protofibrils, resulting in haemostasis. It is theorized that the mechanical effect of the fibrin clot is caused by the polymeric protofibrils between crosslinks, or to their dynamics on a nanoscale order. Despite a number of studies, however, it is still unknown, how the nanoscale protofibril dynamics affect the formation of the macro-scale fibrin clot and thus its mechanical properties. A mesoscopic framework would be useful to tackle this multi-scale problem, but it has not yet been established. We thus propose a minimal mesoscopic model for protofibrils based on Brownian dynamics, and performed numerical simulations of protofibril aggregation. We also performed stretch tests of polymeric protofibrils to quantify the elasticity of fibrin clots. Our model results successfully captured the conformational properties of aggregated protofibrils, e.g., strain-hardening response. Furthermore, the results suggest that the bending stiffness of individual protofibrils increases to resist extension.