SUMMARY

Blood clotting disorders prevent the body's natural ability to achieve hemostasis and lead to bleeding, stroke or heart attack. Understanding the underlying physics behind the clotting process is essential to developing diagnostic tools and treatments for blood-related disorders. Microscale interactions between platelets and fibrin network lead to macroscopic blood clot retraction, a highly complex multiscale process taking place in blood flow.

In this study, a mesoscale model of blood clot contraction based on fundamental platelet-fibrin interaction using dissipative particle dynamics (DPD) method is developed to fully reveal the clot contraction process where platelets movements on a fibrin mesh can be amplified 10,000 fold to shrink the fibrin scaffold to less than 10% of the initial volume. Starting from platelet-fibrin clot, we study how platelet fibrin interaction affects clot contraction and identify the importance of temporal heterogeneity in platelets to clot contraction. Our model recapitulates key emergent behaviors of platelets in clots, such as clustering and fibrin orientation, and successfully predicted clot contraction over three orders of magnitude of platelet concentrations and matched previous clot force data for the first time. We also study how fibrin properties such as initial fibrinogen concentration, length and elasticity of fibrin filament, degree of branching and extent of cross-linking would affect clot contraction. The final stage of this proposed work is to complete modeling of clotting process under blood flow in blood vessels. We aim to elucidate crucial parameters and quantify their effects on blood clotting process that brings insights to disease diagnose and new treatment related with blood clotting disorders. More broadly, the model can also be adapted and modified to study other cell contracting mesh systems such as myofibroblasts.