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A bio-inspired method for direct measurement of local wall shear rates with micrometer localization using the multimeric protein von Willebrand factor as sensor molecule

机译:一种生物启发的方法以多聚体蛋白von Willebrand因子作为传感器分子通过千分尺定位直接测量局部壁的剪切速率

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摘要

Wall shear rates are critical for a broad variety of fluidic phenomena and are taken into account in nearly every experimental or simulation study. Generally, shear rates are not observable directly but rather derived from other parameters such as pressure and flow, often assuming somehow idealized systems. However, there is a biological system which is able to constantly measure the wall shear as a part of a regulatory circuit: The blood circulation system takes advantage of shear rate sensor (protein)molecules (multimeric forms of von Willebrand Factor, VWF), which are dissolved in the blood plasma and dramatically change their conformation under shear conditions. The conformational changes are accompanied by several functional variations and therefore interplay with the regulation of the coagulation system. In this study, we use a recombinantly produced and therefore well-defined multimeric form of VWF as a sensor which directly responds to shear rates. Shear rates, up to 32.000 s−1, were obtained using a kind of micro-plate-to-plate rheometer capable of adsorbing shear-stretched VWF oligomeric molecules on a surface to conserve their differently stretched conformation and so allow detection of their elongation by atomic force microscopy. The laminar flow in this geometrically simple device has been characterized by adopting classical fluid dynamical models, in order to ensure well-known, stable shear rates which could be correlated quantitatively with an observed stretching of sensor molecules.
机译:壁面剪切速率对于各种各样的流体现象至关重要,并且几乎在每个实验或模拟研究中都考虑在内。通常,剪切速率不是直接可观察到的,而是从其他参数(例如压力和流量)得出的,通常会采用某种理想化的系统。但是,有一个生物系统能够作为调节回路的一部分不断测量壁切变:血液循环系统利用了剪切速率传感器(蛋白质)分子(von Willebrand Factor,VWF的多聚形式),溶解在血浆中并在剪切条件下显着改变其构象。构象变化伴随着几个功能变化,因此与凝血系统的调节相互作用。在这项研究中,我们使用重组生产的VWF的定义明确的多聚体形式作为直接响应剪切速率的传感器。使用一种微板对板流变仪,能够将剪切拉伸的VWF低聚物分子吸附在表面上,以保留它们不同的拉伸构象和剪切强度,从而获得高达32.000 s -1 的剪切速率。因此可以通过原子力显微镜检查其伸长率。为了确保众所周知的稳定剪切速率,该几何简单设备中的层流特征在于采用经典的流体动力学模型,该剪切速率可以与观察到的传感器分子的拉伸定量相关。

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