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首页> 外文期刊>Bulletin of the American Physical Society >APS -70th Annual Meeting of the APS Division of Fluid Dynamics- Event - Modeling Shear Induced Von Willebrand Factor Binding to Collagen
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APS -70th Annual Meeting of the APS Division of Fluid Dynamics- Event - Modeling Shear Induced Von Willebrand Factor Binding to Collagen

机译：APS-流体动力学APS部门第70届年会-事件-模拟剪切诱导的冯·威勒布兰德因子与胶原蛋白的结合

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摘要

Von Willebrand factor (vWF) is a blood glycoprotein that binds with platelets and collagen on injured vessel surfaces to form clots. VWF bioactivity is shear flow induced: at low shear, binding between VWF and other biological entities is suppressed; for high shear rate conditions – as are found near arterial injury sites – VWF elongates, activating its binding with platelets and collagen. Based on parameters derived from single molecule force spectroscopy experiments, we developed a coarse-grain molecular model to simulate bond formation probability as a function of shear rate. By introducing a binding criterion that depends on the conformation of a sub-monomer molecular feature of our model, the model predicts shear-induced binding, even for conditions where binding is highly energetically favorable. We further investigate the influence of various model parameters on the ability to predict shear-induced binding (vWF length, collagen site density and distribution, binding energy landscape, and slip/catch bond length) and demonstrate parameter ranges where the model provides good agreement with existing experimental data. Our results may be important for understanding vWF activity and also for achieving targeted drug therapy via biomimetic synthetic molecules.
机译：血管性血友病因子（vWF）是一种血液糖蛋白，与受损血管表面的血小板和胶原蛋白结合形成凝块。 VWF的生物活性是由剪切流引起的：在低剪切下，VWF和其他生物实体之间的结合被抑制;对于高剪切速率条件（如在动脉损伤部位附近发现的那样），VWF会伸长，激活其与血小板和胶原蛋白的结合。基于从单分子力谱实验获得的参数，我们开发了一种粗粒分子模型来模拟键形成概率与剪切速率的关系。通过引入依赖于我们模型的亚单体分子特征构象的结合标准，该模型可以预测剪切诱导的结合，即使在结合力非常高的条件下也是如此。我们进一步研究了各种模型参数对预测剪切诱导结合的能力的影响（vWF长度，胶原蛋白位点密度和分布，结合能态以及滑移/捕获键长度），并证明了模型可与现有实验数据。我们的结果对于理解vWF活性以及通过仿生合成分子实现靶向药物治疗可能很重要。

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