Specificity of endothelial cell reorientation in response to cyclic mechanical stretching

Specificity of endothelial cell reorientation in response to cyclic mechanical stretching
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DOI:
10.1016/s0021-9290(01)00150-6
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发表时间:
2001-12-01
影响因子:
2.4
通讯作者:
Yin, FCP
Yin, FCP
中科院分区:
工程技术3区
文献类型:
--
作者:
Wang, JHC;Goldschmidt-Clermont, P;Yin, FCP

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有证据表明,细胞对机械刺激的反应具体取决于施加的刺激类型。例如,当受到流体剪切力时,内皮细胞会沿着流动方向排列。相反,细胞对循环拉伸的反应是远离拉伸方向。然而,这种细胞对齐反应的几个方面仍然有待澄清:(1)细胞对齐是由于实际的细胞重新定向还是选择性细胞分离?(2)所产生的细胞对齐是细胞对伸长或缩短的反应,还是两者都有?(3)细胞对齐取决于伸展幅度或速率,还是两者兼而有之?最后,肌动蛋白细胞骨架和微管在细胞排列反应中的作用尚不清楚。为了解决这些问题,我们在可变形的硅胶膜上培养人主动脉内皮细胞,并对其进行三种类型的循环拉伸:简单拉伸、纯单轴拉伸和等双向拉伸。对拉伸前后的相同细胞的检查表明,它们重新定向了。无论是简单拉伸还是纯单轴拉伸,细胞都会朝着底物变形最小的方向重新定向,即使两种拉伸的方向只有大约20度的差异。在可比较的拉伸持续时间下,细胞重定向的程度与拉伸幅度的关系比拉伸速率更密切。在任一种拉伸下,内皮细胞的肌动蛋白细胞骨架被重组成平行排列的肌动蛋白细丝(即应力纤维),沿着最小底物变形的方向排列。此外,作为对等双向拉伸的响应,肌动蛋白细胞骨架被重塑为“帐篷状”结构,最终定向到膜平面外-再次朝着最小底物变形的方向。废除微管既不能阻止应力纤维的形成,也不能阻止细胞重定向。因此,内皮细胞对施加在它们身上的变形类型作出非常特异的反应。(C)2001爱思唯尔科学有限公司。保留所有权利。
Evidence suggests that cellular responses to mechanical stimuli depend specifically on the type of stimuli imposed. For example, when subjected to fluid shear stress, endothelial cells align along the flow direction. In contrast, in response to cyclic stretching, cells align away from the stretching direction. However, a few aspects of this cell alignment response remain to be clarified: (1) Is the cell alignment due to actual cell reorientation or selective cell detachment? (2) Does the resulting cell alignment represent a response of the cells to elongation or shortening, or both? (3) Does the cell alignment depend on the stretching magnitude or rate, or both? Finally, the role of the actin cytoskeleton and microtubules in the cell alignment response remains unclear. To address these questions, we grew human aortic endothelial cells on deformable silicone membranes and subjected them to three types of cyclic stretching: simple elongation, pure uniaxial stretching and equi-biaxial stretching. Examination of the same cells before and after stretching revealed that they reoriented. Cells subjected to either simple elongation or pure uniaxial stretching reoriented specifically toward the direction of minimal substrate deformation, even though the directions for the two types of stretching differed by only about 20 degrees. At comparable stretching durations, the extent of cell reorientation was more closely related to the stretching magnitude than the stretching rate. The actin cytoskeleton of the endothelial cell subjected to either type of stretching was reorganized into parallel arrays of actin filaments (i.e., stress fibers) aligned in the direction of the minimal substrate deformation. Furthermore, in response to equi-biaxial stretching, the actin cytoskeleton was remodeled into a "tent-like" structure oriented out of the membrane plane-again towards the direction of the minimal substrate deformation, Finally. abolishing microtubules prevented neither the formation of stress fibers nor cell reorientation. Thus, endothelial cells respond very specifically to the type of deformation imposed upon them. (C) 2001 Elsevier Science Ltd. All rights reserved.