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上皮层顶点的空间波动:Rho 通路调控的量化分析。

Spatial Fluctuations at Vertices of Epithelial Layers: Quantification of Regulation by Rho Pathway.

机构信息

DAMTP, Centre for Mathematical Sciences, University of Cambridge, Cambridge, United Kingdom; Laboratoire Matière et Systèmes Complexes, UMR 7057 CNRS/P7, Université Paris Diderot, Paris cedex 13, France.

Laboratory of Cell Physics, ISIS/IGBMC, Université de Strasbourg and CNRS (UMR 7006), Strasbourg, France; Development and Stem Cells Program, IGBMC, CNRS (UMR 7104), INSERM (U964), Université de Strasbourg, Illkirch, France; School of Mechanical, Materials and Energy Engineering, Indian Institute of Technology, Ropar, India.

出版信息

Biophys J. 2018 Feb 27;114(4):939-946. doi: 10.1016/j.bpj.2017.12.026.

Abstract

In living matter, shape fluctuations induced by acto-myosin are usually studied in vitro via reconstituted gels, whose properties are controlled by changing the concentrations of actin, myosin, and cross-linkers. Such an approach deliberately avoids consideration of the complexity of biochemical signaling inherent to living systems. Acto-myosin activity inside living cells is mainly regulated by the Rho signaling pathway, which is composed of multiple layers of coupled activators and inhibitors. Here, we investigate how such a pathway controls the dynamics of confluent epithelial tissues by tracking the displacements of the junction points between cells. Using a phenomenological model to analyze the vertex fluctuations, we rationalize the effects of different Rho signaling targets on the emergent tissue activity by quantifying the effective diffusion coefficient, and the persistence time and length of the fluctuations. Our results reveal an unanticipated correlation between layers of activation/inhibition and spatial fluctuations within tissues. Overall, this work connects regulation via biochemical signaling with mesoscopic spatial fluctuations, with potential application to the study of structural rearrangements in epithelial tissues.

摘要

在生命物质中,由肌动球蛋白诱导的形状波动通常通过重构凝胶在体外进行研究,其性质通过改变肌动蛋白、肌球蛋白和交联剂的浓度来控制。这种方法故意避免考虑生命系统固有的生化信号的复杂性。活细胞内的肌动球蛋白活性主要受 Rho 信号通路的调节,该通路由多层偶联的激活剂和抑制剂组成。在这里,我们通过跟踪细胞之间连接点的位移来研究这种途径如何控制细胞连接的上皮组织的动力学。使用一种唯象模型来分析顶点波动,我们通过量化有效扩散系数以及波动的持续时间和长度,合理化不同 Rho 信号靶标对出现的组织活性的影响。我们的结果揭示了激活/抑制层与组织内空间波动之间出人意料的相关性。总的来说,这项工作将通过生化信号的调节与介观空间波动联系起来,这可能对研究上皮组织的结构重排具有应用价值。

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本文引用的文献

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Nat Commun. 2016 Oct 14;7:13120. doi: 10.1038/ncomms13120.
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Forcing cells into shape: the mechanics of actomyosin contractility.迫使细胞变形:肌动球蛋白收缩力的力学。
Nat Rev Mol Cell Biol. 2015 Aug;16(8):486-98. doi: 10.1038/nrm4012. Epub 2015 Jul 1.

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