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<p>Mechanisms of blood clot contraction – platelet-driven fibrin network remodeling, are not fully understood. We developed a detailed computational <i>ClotDynaMo</i> model of fibrin network with activated platelets, whose clot contraction rate for normal 450,000/µl human platelets depends on serum viscosity <i>η</i>, platelet filopodia length <i>l</i>, and weakly depends on filopodia traction force <i>f</i> and filopodia extension-retraction speed <i>v</i>. Final clot volume is independent of <i>η</i>, but depends on <i>v</i>, <i>f</i> and <i>l</i>. Analysis of <i>ClotDynaMo</i> 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, <i>η</i> and <i>l</i>. The <i>ClotDynaMo</i> and continuum models can be extended to include red blood cells, variable platelet properties, and mechanics of fibrin network.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月24日

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  • Evgenii Kliuchnikov,
  • Alina D. Peshkova,
  • Minh Quan Vo,
  • Kenneth A. Marx,
  • Rustem I. Litvinov,
  • John W. Weisel,
  • Prashant K. Purohit,
  • Valeri Barsegov

摘要

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.