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一种用于Rho GTP酶介导的细胞极化的机械化学模型。

A mechanochemical model for rho GTPase mediated cell polarization.

作者信息

Kopfer Kai H, Jäger Willi, Matthäus Franziska

机构信息

Frankfurt Institute for Advanced Studies, 60438, Germany.

University of Heidelberg, Interdisciplinary Center for Scientific Computing, Heidelberg 69120, Germany.

出版信息

J Theor Biol. 2020 Nov 7;504:110386. doi: 10.1016/j.jtbi.2020.110386. Epub 2020 Jul 9.

Abstract

Directed motility of eukaryotic cells requires the polarization of the actomyosin cytoskeleton. In many cell types the polar alignment of the actomyosin cytoskeleton occurs in response to a front-rear symmetry break of active Rho GTPase. Experimental evidence in neutrophils indicates that membrane tension plays an important role in the confinement of active Rac to the front domain. We suggest a mechanochemical model for polarization, including Rho GTPase mediated actomyosin cytoskeleton dynamics and changes in membrane tension as an upstream controller of Rho GTP that reflects this observation. The model comprises the Rho GTPases Rac and RhoA which can become activated in response to external signals. The active states regulate the actomyosin mechanics. The model cell is considered as a thin, effectively two dimensional, sheet adhering to a flat substrate. Morphological changes of the actomyosin cytoskeleton induce changes in membrane tension. We numerically show that the model exhibits key features of neutrophil polarization. The model accounts for a simple mechanochemical circuit with the ability to generate robust polarity patterns, wherein cell mechanics serve as a long range signal transmitter.

摘要

真核细胞的定向运动需要肌动球蛋白细胞骨架的极化。在许多细胞类型中,肌动球蛋白细胞骨架的极向排列是对活性Rho GTP酶前后对称性破坏的反应。中性粒细胞的实验证据表明,膜张力在将活性Rac限制在前结构域中起重要作用。我们提出了一个极化的机械化学模型,包括Rho GTP酶介导的肌动球蛋白细胞骨架动力学以及作为反映这一观察结果的Rho GTP上游控制器的膜张力变化。该模型包括Rho GTP酶Rac和RhoA,它们可响应外部信号而被激活。活性状态调节肌动球蛋白力学。模型细胞被视为附着在平坦基质上的薄的、有效的二维薄片。肌动球蛋白细胞骨架的形态变化会引起膜张力的变化。我们通过数值模拟表明该模型展现出中性粒细胞极化的关键特征。该模型解释了一个简单的机械化学回路,该回路具有产生稳健极性模式的能力,其中细胞力学充当长程信号发射器。

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