Schneider S W, Nuschele S, Wixforth A, Gorzelanny C, Alexander-Katz A, Netz R R, Schneider M F
Department of Dermatology, University of Münster, Von-Esmarch-Strasse 58, 48149 Münster, Germany.
Proc Natl Acad Sci U S A. 2007 May 8;104(19):7899-903. doi: 10.1073/pnas.0608422104. Epub 2007 Apr 30.
von Willebrand factor (VWF), a protein present in our circulatory system, is necessary to stop bleeding under high shear-stress conditions as found in small blood vessels. The results presented here help unravel how an increase in hydrodynamic shear stress activates VWF's adhesion potential, leading to the counterintuitive phenomena of enhanced adsorption rate under strong shear conditions. Using a microfluidic device, we were able to mimic a wide range of bloodflow conditions and directly visualize the conformational dynamics of this protein under shear flow. In particular, we find that VWF displays a reversible globule-stretch transition at a critical shear rate gamma(crit) in the absence of any adsorbing surface. Computer simulations reproduce this sharp transition and identify the large size of VWF's repeating units as one of the keys for this unique hydrodynamic activation. In the presence of an adsorbing collagen substrate, we find a large increase in the protein adsorption at the same critical shear rate, suggesting that the globule unfolding in bulk triggers the surface adsorption in the case of a collagen substrate, which provides a sufficient density of binding sites. Monitoring the adsorption process of multiple VWF fibers, we were able to follow the formation of an immobilized network that constitutes a "sticky" grid necessary for blood platelet adhesion under high shear flow. Because areas of high shear stress coincide with a higher chance for vessel wall damage by mechanical forces, we identified the shear-induced increase in the binding probability of VWF as an effective self-regulating repair mechanism of our microvascular system.
血管性血友病因子（VWF）是一种存在于我们循环系统中的蛋白质，在小血管中发现的高剪切应力条件下止血是必需的。此处呈现的结果有助于揭示流体动力剪切应力的增加如何激活VWF的粘附潜力，从而导致在强剪切条件下吸附速率增强这一违反直觉的现象。使用微流体装置，我们能够模拟广泛的血流条件，并直接观察这种蛋白质在剪切流下的构象动力学。特别是，我们发现VWF在没有任何吸附表面的情况下，在临界剪切速率γ（crit）处显示出可逆的球状-伸展转变。计算机模拟重现了这种急剧转变，并确定VWF重复单元的大尺寸是这种独特的流体动力激活的关键之一。在存在吸附性胶原蛋白底物的情况下，我们发现在相同的临界剪切速率下蛋白质吸附大幅增加，这表明在胶原蛋白底物的情况下，本体中的球状展开触发了表面吸附，胶原蛋白底物提供了足够密度的结合位点。监测多个VWF纤维的吸附过程，我们能够追踪固定网络的形成，该网络构成了高剪切流下血小板粘附所需的“粘性”网格。由于高剪切应力区域与机械力导致血管壁损伤的可能性更高相吻合，我们将VWF结合概率的剪切诱导增加确定为我们微血管系统的一种有效的自我调节修复机制。
