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.

中文翻译：

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过去的基质刚度会启动上皮细胞并通过机械记忆调节其未来的集体迁移

在形态发生和癌症转移过程中，成群的细胞会通过刚度不同的组织迁移。尽管已经充分认识到基质刚度对细胞机械敏感性和运动性的影响，但是在细胞转移到新的微环境后，这些依赖于基质的细胞特征是否仍然存在仍是未知的。在这里，我们询问以给定的基质刚度启动上皮细胞是否会影响它们将来在不同基质上的集体迁移-我们将这一特性称为迁移细胞的“机械记忆”。为了在定义的基质上灌注细胞并跟踪其集体迁移到刚度不同的相邻次级基质上，我们通过逐步聚合不同PA组合物来开发模块化聚丙烯酰胺底物。我们报告说，与其在均质软基质上的控制行为相比，硬基质上的上皮细胞迁移更快，表现出更高的肌动球蛋白表达，形成更大的粘着斑并保留核YAP，即使到达软次级基质上也是如此。在软ECM上灌注会产生相反的效果。YAP的耗尽极大地减少了这种依赖于内存的迁移。我们的结果提出了过去的基质刚度对机械敏感的集体细胞迁移的先前未知的调节，其中机械记忆取决于YAP活性。YAP的耗尽极大地减少了这种依赖于内存的迁移。我们的结果提出了过去的基质刚度对机械敏感的集体细胞迁移的先前未知的调节，其中机械记忆取决于YAP活性。YAP的耗尽极大地减少了这种依赖于内存的迁移。我们的结果提出了过去的基质刚度对机械敏感的集体细胞迁移的先前未知的调节，其中机械记忆取决于YAP活性。