The human brain microvasculature is constantly exposed to variable fluid flow regimes and their influence on the endothelium depends in part on the synchronous cooperative behavior between cell–cell junctions and the cytoskeleton. In this study, we exposed human cerebral microvascular endothelial cells to a low laminar flow (1 dyne⋅cm⁻²), high laminar flow (10 dyne⋅cm⁻²), low oscillatory flow (±1 dyne⋅cm⁻²), or high oscillatory flow (±10 dyne⋅cm⁻²) for 24 hr. After this time, endothelial cell–cell junction and cytoskeletal structural response was characterized through observation of zonula occludens-1 (ZO-1), claudin-5, junctional adhesion molecule-A (JAM-A), vascular endothelial cadherin (VE-Cad), and F-actin. In addition, we also characterized cell morphology through measurement of cell area and cell eccentricity. Our results revealed the greatest change in junctional structure reorganization for ZO-1 and JAM-A to be observed under low laminar flow conditions while claudin-5 exhibited the greatest change in structural reorganization under both low and high laminar flow conditions. However, VE-Cad displayed the greatest structural response under a high laminar flow, reflecting the unique responses each cell–cell junction protein had to each fluid flow regime. In addition, cell area and cell eccentricity displayed most significant changes under the high laminar flow and low oscillatory flow, respectively. We believe this study will be useful to the field of cell mechanics and mechanobiology.

中文翻译：

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可变流体流动状态改变人脑微血管内皮细胞-细胞连接和细胞骨架结构

人脑微脉管系统不断暴露于可变的流体流动状态，它们对内皮的影响部分取决于细胞 - 细胞连接和细胞骨架之间的同步协作行为。在这项研究中，我们将人脑微血管内皮细胞暴露于低层流 (1 dyne⋅cm ^-2 )、高层流 (10 dyne⋅cm ^-2 )、低振荡流 (±1 dyne⋅cm ^-2 )、或高振荡流（±10 dyne⋅cm ^-2) 24 小时。此后，通过观察zonula occludens-1 (ZO-1)、claudin-5、连接粘附分子-A (JAM-A)、血管内皮钙粘蛋白(VE-Cad)来表征内皮细胞-细胞连接和细胞骨架结构反应) 和 F-肌动蛋白。此外，我们还通过测量细胞面积和细胞离心率来表征细胞形态。我们的结果显示，在低层流条件下，ZO-1 和 JAM-A 的结结构重组变化最大，而 Claudin-5 在低层流和高层流条件下的结构重组变化最大。然而，VE-Cad 在高层流下表现出最大的结构响应，反映了每个细胞-细胞连接蛋白对每个流体流动状态的独特响应。此外，细胞面积和细胞离心率分别在高层流和低振荡流下表现出最显着的变化。我们相信这项研究将对细胞力学和机械生物学领域有用。