A Continuum Model for the Unfolding of von Willebrand Factor.
A Continuum Model for the Unfolding of von Willebrand Factor.
复制标题
冯维勒布兰德因子展开的连续体模型。
DOI：
10.1007/s10439-021-02845-5
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发表时间：
2021-09
影响因子：
3.8
通讯作者：
Antaki, James F.
中科院分区：
文献类型：
--
作者：
Zhussupbekov, Mansur;Mendez Rojano, Rodrigo;Wu, Wei-Tao;Massoudi, Mehrdad;Antaki, James F.
关键词：
血管性血友病因子是一种在血液中循环的机械敏感性蛋白质，其介导血小板粘附于内皮下胶原和在高剪切速率下的血小板聚集。它的止血功能和血栓形成作用，以及对酶裂解的敏感性，由从塌陷球状状态到拉伸状态的构象变化来调节。因此，在模拟vWF介导的血栓形成或vWF降解时，必须考虑vWF多聚体的构象。我们介绍了一个连续模型的vWF展开的框架内，我们的多成分模型的血小板介导的血栓形成。该模型考虑了两个相互转化的vWF物种对应的折叠和拉伸构象状态。vWF展开通过两种方式发生：简单剪切中的翻滚和具有主导拉伸分量的流动中的强烈展开。这两个制度被证明在平行板之间的Couette流和在交叉槽几何形状的拉伸流。然后在设计用于诱导高剪切vWF介导的血栓形成和筛选血管性血友病的几种微流体系统中验证vWF解折叠模型。该模型预测在实验观察到闭塞性血栓形成的关键区域中高浓度的拉伸vWF。拉伸流引起的强展开仅限于通道的中心轴或中间平面，而通道壁附近的vWF展开依赖于剪切翻滚机制。在这项工作中提出的vWF展开的连续模型可以用于在复杂的几何形状的vWF介导的血栓形成或vWF降解的数值模拟。然而，将模型扩展到3-D任意流动和湍流将带来相当大的挑战。
von Willebrand Factor is a mechano-sensitive protein circulating in blood that mediates platelet adhesion to subendothelial collagen and platelet aggregation at high shear rates. Its hemostatic function and thrombogenic effect, as well as susceptibility to enzymatic cleavage, are regulated by a conformational change from a collapsed globular state to a stretched state. Therefore, it is essential to account for the conformation of the vWF multimers when modeling vWF-mediated thrombosis or vWF degradation. We introduce a continuum model of vWF unfolding that is developed within the framework of our multi-constituent model of platelet-mediated thrombosis. The model considers two interconvertible vWF species corresponding to the collapsed and stretched conformational states. vWF unfolding takes place via two regimes: tumbling in simple shear and strong unfolding in flows with dominant extensional component. These two regimes were demonstrated in a Couette flow between parallel plates and an extensional flow in a cross-slot geometry. The vWF unfolding model was then verified in several microfluidic systems designed for inducing high-shear vWF-mediated thrombosis and screening for von Willebrand Disease. The model predicted high concentration of stretched vWF in key regions where occlusive thrombosis was observed experimentally. Strong unfolding caused by the extensional flow was limited to the center axis or middle plane of the channels, whereas vWF unfolding near the channel walls relied upon the shear tumbling mechanism. The continuum model of vWF unfolding presented in this work can be employed in numerical simulations of vWF-mediated thrombosis or vWF degradation in complex geometries. However, extending the model to 3-D arbitrary flows and turbulent flows will pose considerable challenges.
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影响因子：
4.4
作者：
Jendrejack, RM;de Pablo, JJ;Graham, MD
通讯作者：
Graham, MD
DOI：
10.1016/j.ijengsci.2010.09.003
发表时间：
2010-11-01
影响因子：
6.6
作者：
Hund SJ;Antaki JF;Massoudi M
通讯作者：
Massoudi M
影响因子：
7.5
作者：
Kragh, Thorsten;Napoleone, Marina;Reininger, Armin J.
通讯作者：
Reininger, Armin J.
影响因子：
3.1
作者：
DUNLAP, PN;LEAL, LG
通讯作者：
LEAL, LG
影响因子：
1.8
作者：
Alexander-Katz, A.;Netz, R. R.
通讯作者：
Netz, R. R.