SUMMARY

This thesis develops a mesoscale blood clot model based on dissipative particle dynamics to investigate blood clot contraction biophysics by directly linking the microscale cell movements to the macroscale clot behaviors. The computational model based only on biophysical measurements of platelets, fibrin networks, and red blood cells (RBCs) strongly agrees with experimental bulk clot contraction data. Focusing on identifying the essential parameters and mechanics of clot contraction, we systematically investigate the effects of single platelet properties and dynamics, heterogeneity of platelets in clotting environment, clot forming conditions, and fibrin network properties on clot contraction. Our work provides highly detailed information at different spatial and temporal scales about the clot contraction kinetics and dynamics. We show that the collective microscopic movements of platelets in fibrin scaffolds mediate the significant macroscopic changes in bulk clots, resulting in dramatic decrease in clot size and increase in clot stiffness. We discover that platelets utilize the heterogeneity in their onset and filopodia retraction timing to enhance volumetric material contraction and magnify contractile forces, indicating that cell heterogeneity carry an essential biophysical function. Our work reveals the mechanism by which platelets induce forces in bulk clots and provides a relationship between platelet force and clot force, applicable to various physiological clot configurations and attachment conditions. Furthermore, our work reveals the interactions between contracting fibrin-platelet clots with RBCs and flow, and the evolutions of final thrombi structures observed experimentally. We discover the existence of a critical initial clot size that allows RBC entrapment, and show that RBC retention and compaction in thrombi can be solely a result of the mechanistic contraction of the clot without additional binding or adhesive interactions. We show that RBC retention hinders the contraction process and results in larger final clots, while the expulsion of RBCs located closer to clot outer surface results in the emergence of a dense fibrin shell enveloping the clot.