Thrombin flux and wall shear rate regulate fibrin fiber deposition state during polymerization under flow

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Abstract

Thrombin is released as a soluble enzyme from the surface of platelets and tissue-factor-bearing cells to trigger fibrin polymerization during thrombosis under flow conditions. Although isotropic fibrin polymerization under static conditions involves protofibril extension and lateral aggregation leading to a gel, factors regulating fiber growth are poorly quantified under hemodynamic flow due to the difficulty of setting thrombin fluxes. A membrane microfluidic device allowed combined control of both thrombin wall flux (10-13 to 10-11 nmol/μm2 s) and the wall shear rate (10-100 s-1) of a flowing fibrinogen solution. At a thrombin flux of 10 -12 nmol/μ2 s, both fibrin deposition and fiber thickness decreased as the wall shear rate increased from 10 to 100 s -1. Direct measurement and transport-reaction simulations at 12 different thrombin flux-wall shear rate conditions demonstrated that two dimensionless numbers, the Peclet number (Pe) and the Damkohler number (Da), defined a state diagram to predict fibrin morphology. For Da < 10, we only observed thin films at all Pe. For 10 < Da < 900, we observed either mat fibers or gels, depending on the Pe. For Da > 900 and Pe < 100, we observed three-dimensional gels. These results indicate that increases in wall shear rate quench first lateral aggregation and then protofibril extension. © 2010 by the Biophysical Society.

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Neeves, K. B., Illing, D. A. R., & Diamond, S. L. (2010). Thrombin flux and wall shear rate regulate fibrin fiber deposition state during polymerization under flow. Biophysical Journal, 98(7), 1344–1352. https://doi.org/10.1016/j.bpj.2009.12.4275

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