Past matrix stiffness primes epithelial cells and regulates their future collective migration through a mechanical memory.
Past matrix stiffness primes epithelial cells and regulates their future collective migration through a mechanical memory.
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DOI：
10.1016/j.biomaterials.2017.09.012
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发表时间：
2017-11
期刊：
影响因子：
14
通讯作者：
Pathak A
中科院分区：
文献类型：
--
作者：
Nasrollahi S;Walter C;Loza AJ;Schimizzi GV;Longmore GD;Pathak A
在形态发生和肿瘤转移过程中，成组细胞在不同硬度的组织中迁移。虽然基质刚度对细胞力学敏感性和运动性的影响已经得到了很好的认识，但这些依赖基质的细胞特征在细胞移动到新的微环境后是否仍然存在仍是未知的。在这里，我们研究了上皮细胞在给定基质硬度下的启动是否会影响它们未来在不同基质上的集体迁移——我们将这种特性称为迁移细胞的“机械记忆”。为了在确定的基质上初始化细胞，并跟踪它们集体迁移到相邻的不同刚度的次级基质上，我们通过逐步聚合不同的PA成分开发了模块化聚丙烯酰胺底物。我们报道，与在均质软基质上的对照行为相比，在坚硬基质上启动的上皮细胞迁移更快，表现出更高的肌动球蛋白表达，形成更大的局灶粘连，并且在到达软次级基质后仍保留核YAP。在软ECM上启动会产生相反的效果。YAP的耗尽极大地减少了这种依赖于内存的迁移。我们的研究结果提出了一种以前未确定的通过过去的基质刚度对机械敏感的集体细胞迁移的调节，其中机械记忆取决于YAP活性。
During morphogenesis and cancer metastasis, grouped cells migrate through tissues of dissimilar stiffness. Although the influence of matrix stiffness on cellular mechanosensitivity and motility are well-recognized, it remains unknown whether these matrix-dependent cellular features persist after cells move to a new microenvironment. Here, we interrogate whether priming of epithelial cells by a given matrix stiffness influences their future collective migration on a different matrix – a property we refer to as the ‘mechanical memory’ of migratory cells. To prime cells on a defined matrix and track their collective migration onto an adjoining secondary matrix of dissimilar stiffness, we develop a modular polyacrylamide substrate through step-by-step polymerization of different PA compositions. We report that epithelial cells primed on a stiff matrix migrate faster, display higher actomyosin expression, form larger focal adhesions, and retain nuclear YAP even after arriving onto a soft secondary matrix, as compared to their control behavior on a homogeneously soft matrix. Priming on a soft ECM causes a reverse effect. The depletion of YAP dramatically reduces this memory-dependent migration. Our results present a previously unidentified regulation of mechanosensitive collective cell migration by past matrix stiffness, in which mechanical memory depends on YAP activity.
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DOI：
10.1083/jcb.201505105
发表时间：
2016-01-18
期刊：
The Journal of cell biology
影响因子：
--
作者：
Plutoni C;Bazellieres E;Le Borgne-Rochet M;Comunale F;Brugues A;Séveno M;Planchon D;Thuault S;Morin N;Bodin S;Trepat X;Gauthier-Rouvière C
通讯作者：
Gauthier-Rouvière C
影响因子：
9.2
作者：
Codelia, Veronica A.;Sun, Gongping;Irvine, Kenneth D.
通讯作者：
Irvine, Kenneth D.
影响因子：
21.3
作者：
Das, Tamal;Safferling, Kai;Spatz, Joachim P.
通讯作者：
Spatz, Joachim P.
DOI：
10.1007/978-1-62703-056-4_15
发表时间：
2013-01-01
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Mackay, Joanna L;Kumar, Sanjay
通讯作者：
Kumar, Sanjay
影响因子：
21.3
作者：
通讯作者：
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