Epithelia have distinct cellular architectures, which are established in development, re-established after wounding, and maintained during tissue homeostasis despite cell turnover and mechanical perturbations. In turn, cell shape also controls tissue function as a regulator of cell differentiation, proliferation, and motility. Here we investigate cell shape changes in a model epithelial monolayer. After the onset of confluence, cells continue to proliferate and change shape over time, eventually leading to a final architecture characterized by arrested motion and more regular cell shapes. Such monolayer remodeling is robust, with qualitatively similar evolution in cell shape and dynamics observed across disparate perturbations. Here we quantify differences in monolayer remodeling guided by the active vertex model to identify underlying order parameters controlling epithelial architecture. When monolayers are formed atop extracellular matrix with varied stiffness, we find the cell density at which motion arrests varies significantly but the cell shape remains constant, consistent with the onset of tissue rigidity. In contrast, pharmacological perturbations can significantly alter the cell shape at which tissue dynamics is arrested, consistent with varied amounts of active stress within the tissue. Across all experimental conditions the final cell shape is well correlated to the cell proliferation rate, and cell cycle inhibition immediately arrests cell motility. Finally, we demonstrate cell-cycle variation in junctional tension as a source of active stress within the monolayer. Thus, the architecture and mechanics of epithelial tissue can arise from an interplay between cell mechanics and stresses arising from cell cycle dynamics.

中文翻译：

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细胞周期依赖性主动应激驱动上皮细胞重塑

上皮细胞具有独特的细胞结构，尽管细胞更新和机械扰动，但它们在发育中已经建立，在受伤后得以重新建立，并在组织动态平衡期间得以维持。反过来，细胞形状也控制组织功能，作为细胞分化，增殖和运动的调节剂。在这里，我们调查模型上皮单层细胞形状的变化。融合开始后，细胞会继续增殖并随着时间的推移而改变形状，最终导致最终的结构以停滞的运动和更规则的细胞形状为特征。这种单层重塑是鲁棒的，跨不同的扰动观察到细胞形状和动力学的定性相似的演变。在这里，我们量化由主动顶点模型指导的单层重塑中的差异，以识别控制上皮结构的基本顺序参数。当单层形成在具有变化的刚度的细胞外基质之上时，我们发现运动停止明显变化但细胞形状保持恒定的细胞密度，这与组织刚度开始一致。相反，药理学扰动可以显着改变组织动力学受阻的细胞形状，这与组织内活动应力的变化量一致。在所有实验条件下，最终的细胞形状与细胞增殖速率密切相关，并且细胞周期抑制立即阻止细胞运动。最后，我们证明了细胞周期变化的连接张力作为单层内活动应力的来源。因此，上皮组织的结构和力学可以由细胞力学与细胞周期动力学产生的压力之间的相互作用产生。