Thrombin Flux and Wall Shear Rate Regulate Fibrin Fiber Deposition State during Polymerization under Flow
Thrombin Flux and Wall Shear Rate Regulate Fibrin Fiber Deposition State during Polymerization under Flow
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DOI：
10.1016/j.bpj.2009.12.4275
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发表时间：
2010-04-07
影响因子：
3.4
通讯作者：
Diamond, S. L.
中科院分区：
文献类型：
--
作者：
Neeves, K. B.;Illing, D. A. R.;Diamond, S. L.
凝血酶作为可溶性酶从血小板和携带组织因子的细胞表面释放，以在流动条件下血栓形成期间触发纤维蛋白聚合。虽然在静态条件下的各向同性纤维蛋白聚合涉及原纤维延伸和侧向聚集，导致凝胶，调节纤维生长的因素，由于难以设置凝血酶流量的血液动力学流动下量化不佳。膜微流体装置允许流动的纤维蛋白原溶液的凝血酶壁通量（10（-13）至10（-11）nmol/μ m（2）s）和壁剪切速率（10-100 s（-1））的组合控制。当凝血酶流量为10（-12）nmol/μ m（2）s时，纤维蛋白沉积和纤维厚度均随壁面剪切速率从10 s（-1）增加到100 s（-1）而减小。直接测量和运输反应模拟在12个不同的凝血酶流量壁剪切速率条件下表明，两个无量纲的数字，Peclet数（Pe）和Damkohler数（Da），定义了一个状态图来预测纤维蛋白形态。对于Da < 10，我们在所有Pe下仅观察到薄膜。对于10 < Da < 900，我们观察到垫纤维或凝胶，这取决于Pe。对于Da > 900和Pe < 100，我们观察到三维凝胶。这些结果表明，壁剪切速率的增加首先淬灭横向聚集，然后淬灭原纤维延伸。
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/mu m(2) s) and the wall shear rate (10-100 s(-1)) of a flowing fibrinogen solution. At a thrombin flux of 10(-12) nmol/mu m(2) 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.