Exploring effects of platelet contractility on the kinetics, thermodynamics, and mechanisms of fibrin clot contraction
Evgenii Kliuchnikov, Alina D. Peshkova, Minh Vo, Kenneth A. Marx, Rustem I. Litvinov, John W. Weisel, Prashant K. Purohit, Valeri Barsegov
Abstract
Mechanisms of blood clot contraction – platelet-driven fibrin network remodeling, are not fully understood. We developed a detailed computational ClotDynaMo model of fibrin network with activated platelets, whose clot contraction rate for normal 450,000/µl human platelets depends on serum viscosity η , platelet filopodia length l , and weakly depends on filopodia traction force f and filopodia extension-retraction speed v . Final clot volume is independent of η , but depends on v , f and l . Analysis of ClotDynaMo output revealed a 2.24 TJ/mol clot contraction free energy change, with ~67% entropy and ~33% internal energy changes. The results illuminate the “optimal contraction principle” that maximizes volume change while minimizing energy cost. An 8-chain continuum model of polymer elasticity containing platelet forces, captures clot contractility as a function of platelet count, η and l . The ClotDynaMo and continuum models can be extended to include red blood cells, variable platelet properties, and mechanics of fibrin network.