Dynamic mechanisms of cell rigidity sensing: insights from a computational model of actomyosin networks.
Dynamic mechanisms of cell rigidity sensing: insights from a computational model of actomyosin networks.
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DOI：
10.1371/journal.pone.0049174
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Kamm RD
中科院分区：
文献类型：
--
作者：
Borau C;Kim T;Bidone T;García-Aznar JM;Kamm RD
细胞调节自身以响应周围环境，如基质弹性，表现出由细胞骨架的收缩性驱动的结构重组。细胞骨架是真核细胞的支架结构，在许多机械和生物功能中起着核心作用。它由肌动蛋白、肌动蛋白交联蛋白（actin cross-linking proteins，ACP）和分子马达组成。马达通过以极性方式滑动肌动蛋白丝对来产生收缩力，并且已知细胞骨架网络的收缩反应也通过外部刺激（例如基底刚度）来调节。这暗示了肌动球蛋白收缩性在细胞机械感受中的重要作用。然而，细胞如何通过收缩性感知基质硬度仍然是一个悬而未决的问题。在这里，我们提出了一个3-D布朗动力学计算模型的交联肌动蛋白网络，包括分子马达和ACP的动力学。该主动网络的机械传感性能进行了研究，通过评估收缩和应力响应于不同的基板刚度。结果表明，两种机制，以限制内部应力：（i）在刚性基板，电机走，直到他们发挥其最大的力量，导致高原应力是独立的基板刚度，而（ii）在软基板，电机走，直到他们成为其他电机或ACP阻塞，导致次最大应力水平。因此，这项研究为分子马达在细胞收缩和刚性感知中的作用提供了新的见解。
Cells modulate themselves in response to the surrounding environment like substrate elasticity, exhibiting structural reorganization driven by the contractility of cytoskeleton. The cytoskeleton is the scaffolding structure of eukaryotic cells, playing a central role in many mechanical and biological functions. It is composed of a network of actins, actin cross-linking proteins (ACPs), and molecular motors. The motors generate contractile forces by sliding couples of actin filaments in a polar fashion, and the contractile response of the cytoskeleton network is known to be modulated also by external stimuli, such as substrate stiffness. This implies an important role of actomyosin contractility in the cell mechano-sensing. However, how cells sense matrix stiffness via the contractility remains an open question. Here, we present a 3-D Brownian dynamics computational model of a cross-linked actin network including the dynamics of molecular motors and ACPs. The mechano-sensing properties of this active network are investigated by evaluating contraction and stress in response to different substrate stiffness. Results demonstrate two mechanisms that act to limit internal stress: (i) In stiff substrates, motors walk until they exert their maximum force, leading to a plateau stress that is independent of substrate stiffness, whereas (ii) in soft substrates, motors walk until they become blocked by other motors or ACPs, leading to submaximal stress levels. Therefore, this study provides new insights into the role of molecular motors in the contraction and rigidity sensing of cells.
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影响因子：
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