Short-Term Shear Stress Induces Rapid Actin Dynamics in Living Endothelial Cells.
Short-Term Shear Stress Induces Rapid Actin Dynamics in Living Endothelial Cells.
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DOI：
10.3970/mcb.2008.005.247
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Colin K. Choi;B. Helmke
中科院分区：
文献类型：
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作者：
Colin K. Choi;B. Helmke
血流动力学切应力指导血管内皮细胞的多种表型特征，包括细胞形态、细胞骨架结构和基因表达谱。细胞外液体力的感知和处理可能是通过肌动蛋白细胞骨架网络向细胞内信号起始位置的机械传递而介导的。在这项研究中，我们发现肌动蛋白介导的活体牛主动脉内皮细胞(ECs)在单向恒定流体剪切力(15dyn/cm(2))作用下的快速形态变化。在血流开始后的12分钟内，亚汇合流细胞在片层中表现出动态的边缘活动，并在下游和侧向出现小的褶皱，上游方向的活动最小。12min后，周围缘伸展消失。切应力作用下的融合细胞单层在血流开始后仅表现出边缘波动的轻微增加。加入细胞松弛素D来破坏肌动蛋白聚合，可抑制两种融合的EC单层中流动介导的肌动蛋白重塑的幅度。有趣的是，当亚汇合流内皮细胞暴露于两个连续的流动步骤(1dyn/cm(2)和15dyn/cm(2)12分钟后)时，肌动蛋白介导的边缘活动在第二个流动步骤后并没有额外增加。因此，反复的流量增加使肌动蛋白细胞骨架中机械敏感的结构动力学变得不敏感。
Hemodynamic shear stress guides a variety of endothelial phenotype characteristics, including cell morphology, cytoskeletal structure, and gene expression profile. The sensing and processing of extracellular fluid forces may be mediated by mechanotransmission through the actin cytoskeleton network to intracellular locations of signal initiation. In this study, we identify rapid actin-mediated morphological changes in living subconfluent and confluent bovine aortic endothelial cells (ECs) in response to onset of unidirectional steady fluid shear stress (15 dyn/cm(2)). After flow onset, subconfluent cells exhibited dynamic edge activity in lamellipodia and small ruffles in the downstream and side directions for the first 12 min; activity was minimal in the upstream direction. After 12 min, peripheral edge extension subsided. Confluent cell monolayers that were exposed to shear stress exhibited only subtle increases in edge fluctuations after flow onset. Addition of cytochalasin D to disrupt actin polymerization served to suppress the magnitude of flow-mediated actin remodeling in both subconfluent confluent EC monolayers. Interestingly, when subconfluent ECs were exposed to two sequential flow step increases (1 dyn/cm(2) followed by 15 dyn/cm(2) 12 min later), actin-mediated edge activity was not additionally increased after the second flow step. Thus, repeated flow increases served to desensitize mechanosensitive structural dynamics in the actin cytoskeleton.