Exploring effects of platelet contractility on the kinetics, thermodynamics, and mechanisms of fibrin clot contraction.

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.