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耦合机械张力与小GTP酶信号传导以产生细胞和组织动力学。

Coupling mechanical tension and GTPase signaling to generate cell and tissue dynamics.

作者信息

Zmurchok Cole, Bhaskar Dhananjay, Edelstein-Keshet Leah

机构信息

Department of Mathematics, University of British Columbia, Vancouver, BC, Canada.

出版信息

Phys Biol. 2018 Apr 30;15(4):046004. doi: 10.1088/1478-3975/aab1c0.

DOI:10.1088/1478-3975/aab1c0
PMID:29473547
Abstract

Regulators of the actin cytoskeleton such Rho GTPases can modulate forces developed in cells by promoting actomyosin contraction. At the same time, through mechanosensing, tension is known to affect the activity of Rho GTPases. What happens when these effects act in concert? Using a minimal model (1 GTPase coupled to a Kelvin-Voigt element), we show that two-way feedback between signaling ('RhoA') and mechanical tension (stretching) leads to a spectrum of cell behaviors, including contracted or relaxed cells, and cells that oscillate between these extremes. When such 'model cells' are connected to one another in a row or in a 2D sheet ('epithelium'), we observe waves of contraction/relaxation and GTPase activity sweeping through the tissue. The minimal model lends itself to full bifurcation analysis, and suggests a mechanism that explains behavior observed in the context of development and collective cell behavior.

摘要

肌动蛋白细胞骨架的调节因子,如Rho GTPases,可以通过促进肌动球蛋白收缩来调节细胞中产生的力。同时,通过机械传感,已知张力会影响Rho GTPases的活性。当这些效应协同作用时会发生什么?使用一个最小模型(一个与开尔文-维格纳元件耦合的GTPase),我们表明信号传导(“RhoA”)和机械张力(拉伸)之间的双向反馈会导致一系列细胞行为,包括收缩或松弛的细胞,以及在这些极端状态之间振荡的细胞。当这些“模型细胞”彼此排成一排或形成二维薄片(“上皮组织”)连接时,我们观察到收缩/松弛波和GTPase活性波在组织中传播。这个最小模型适合进行完整的分岔分析,并提出了一种机制来解释在发育和集体细胞行为背景下观察到的行为。

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