An Interplay between Matrix Anisotropy and Actomyosin Contractility Regulates 3D-Directed Cell Migration
An Interplay between Matrix Anisotropy and Actomyosin Contractility Regulates 3D-Directed Cell Migration
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DOI：
10.1002/adfm.201702322
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发表时间：
2017-09-20
影响因子：
19
通讯作者：
Samitier, Josep
中科院分区：
文献类型：
--
作者：
Caballero, David;Palacios, Lucas;Samitier, Josep
定向细胞迁移对于许多生物过程至关重要，例如胚胎发育或癌症进展。已知细胞收缩性和对细胞外基质的粘附可调节细胞运动机制。然而，外在因素和内在因素在分子水平上对三维（3D）定向细胞迁移的生物物理机制的交互作用仍不清楚。在这项工作中，细胞外微环境的一种新颖的生理相关体外模型被用来揭示细胞外基质的拓扑各向异性如何与肌动球蛋白收缩性协同作用来调节定向细胞迁移形态动力学。这项研究表明，接种在偏振 3D 基质上的细胞表现出不对称突起形态动力学和体内样表型。研究发现，基质各向异性显着增强了细胞的方向性，但令人惊讶的是，并没有增强细胞的侵袭距离。在 Rho 抑制的细胞中，基质各向异性抵消了肌动球蛋白驱动力的缺乏来稳定细胞方向性，这表明细胞引导的肌球蛋白 II 独立机制。最后，这项研究表明，在各向同性 3D 环境中，细胞方向性与肌动球蛋白收缩性无关。总而言之，这项研究提供了关于定向细胞运动的生物力学调节的新颖定量数据，并显示了基质各向异性和肌动球蛋白力在引导 3D 微环境中细胞迁移的重要调节作用。
Directed cell migration is essential for many biological processes, such as embryonic development or cancer progression. Cell contractility and adhesion to the extracellular matrix are known to regulate cell locomotion machinery. However, the cross-talk between extrinsic and intrinsic factors at the molecular level on the biophysical mechanism of three dimensional (3D)-directed cell migration is still unclear. In this work, a novel physiologically relevant in vitro model of the extracellular microenvironment is used to reveal how the topological anisotropy of the extracellular matrix synergizes with actomyosin contractility to modulate directional cell migration morphodynamics. This study shows that cells seeded on polarized 3D matrices display asymmetric protrusion morphodynamics and in-vivo-like phenotypes. It is found that matrix anisotropy significantly enhances cell directionality, but strikingly, not the invasion distance of cells. In Rho-inhibited cells, matrix anisotropy counteracts the lack of actomyosin-driven forces to stabilize cell directionality suggesting a myosin-II-independent mechanism for cell guidance. Finally, this study shows that on isotropic 3D environments, cell directionality is independent of actomyosin contractility. Altogether, this study provides novel quantitative data on the biomechanical regulation of directional cell motion and shows the important regulatory role of matrix anisotropy and actomyosin forces to guide cell migration in 3D microenvironments.