Despite recent efforts to understand homeostasis in epithelial tissues, there are many unknowns surrounding this steady state. It is considered to be regulated by mechanoresponse, but unlike for single cells, this idea remains heavily debated for tissues. Here, we show that changes in matrix stiffness induce a nonequilibrium transition from tubular to squamous Madin-Darby Canine Kidney II tissues. Nonetheless, despite different cell morphologies and densities, all homeostatic tissues display equivalent topologies, which, hence, must be actively targeted and regulated. On the contrary, the mechanoresponse induces dramatic changes in the large-scale organization of the colonies. On stiff gels, this yields an unreported cooperative state of motile cells displaying higher densities than in the arrested homeostatic state, which suggests a more complex relation between cell density and motility than previously anticipated. Our results unequivocally relate the mechanosensitive properties of individual cells to the evolving macroscopic structures, an effect that could be important for understanding the emergent pathologies of living tissues.

中文翻译：

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上皮组织稳态的机械调节

尽管最近努力了解上皮组织的稳态，但围绕这种稳定状态仍有许多未知数。它被认为是受机械反应调节的，但与单细胞不同，这个想法在组织中仍然存在很大争议。在这里，我们表明基质刚度的变化会导致从管状到鳞状 Madin-Darby Canine Kidney II 组织的非平衡转变。尽管如此，尽管细胞形态和密度不同，但所有稳态组织都显示出等效的拓扑结构，因此必须积极靶向和调节。相反，机械反应会引起菌落大规模组织的巨大变化。在硬凝胶上，这会产生一种未报告的运动细胞协同状态，显示出比停滞稳态更高的密度，这表明细胞密度和运动性之间的关系比以前预期的更复杂。我们的结果明确地将单个细胞的机械敏感特性与不断发展的宏观结构联系起来，这种影响对于理解活组织的紧急病理可能很重要。