A computational model of the response of adherent cells to stretch and changes in substrate stiffness.
A computational model of the response of adherent cells to stretch and changes in substrate stiffness.
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DOI：
10.1152/japplphysiol.00962.2013
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发表时间：
2014-04
影响因子：
3.3
通讯作者：
H. Parameswaran;K. Lutchen;B. Suki
中科院分区：
文献类型：
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作者：
H. Parameswaran;K. Lutchen;B. Suki
体内的细胞存在于一个动态的机械环境中，在这种环境中，它们受到机械拉伸以及潜在细胞外基质(ECM)的组成和硬度的变化。然而，细胞感知和适应动态机械环境，特别是伸展的潜在机制还不是很清楚。在这项研究中，我们假设由非肌肉肌球蛋白II分子马达驱动的主动结构重排引起的肌动蛋白网络水平上的紧急现象在细胞对拉伸和细胞外基质硬度变化的反应中发挥了主要作用。为了验证这一假设，我们引入了一个简单的肌动蛋白-肌球蛋白相互作用的网络模型，该模型将肌动蛋白网络的主动自组织与网络的刚性和网络产生的牵引力联系起来。我们证明，这样的网络不仅复制了基质硬度变化对细胞牵引力和硬度的影响以及细胞的力发展速率与其基质硬度的依赖关系，而且还解释了贴壁细胞对瞬时和循环拉伸的物理反应。我们的结果有力地表明，肌动蛋白-肌球蛋白结构的主动重组所控制的网络现象在细胞机械感知和对细胞外基质硬度和外部机械拉伸的变化的响应中发挥着重要作用。
Cells in the body exist in a dynamic mechanical environment where they are subject to mechanical stretch as well as changes in composition and stiffness of the underlying extracellular matrix (ECM). However, the underlying mechanisms by which cells sense and adapt to their dynamic mechanical environment, in particular to stretch, are not well understood. In this study, we hypothesized that emergent phenomena at the level of the actin network arising from active structural rearrangements driven by nonmuscle myosin II molecular motors play a major role in the cellular response to both stretch and changes in ECM stiffness. To test this hypothesis, we introduce a simple network model of actin-myosin interactions that links active self-organization of the actin network to the stiffness of the network and the traction forces generated by the network. We demonstrate that such a network replicates not only the effect of changes in substrate stiffness on cellular traction and stiffness and the dependence of rate of force development by a cell on the stiffness of its substrate, but also explains the physical response of adherent cells to transient and cyclic stretch. Our results provide strong indication that network phenomena governed by the active reorganization of the actin-myosin structure plays an important role in cellular mechanosensing and response to both changes in ECM stiffness and externally applied mechanical stretch.