Abstract：
The epithelial adaptations to mechanical stress are facilitated by molecular and tissue-scale changes that include the strengthening of junctions, cytoskeletal reorganization, and cell-proliferation-mediated changes in tissue rheology. However, the role of cell size in controlling these properties remains underexplored. Our experiments in the zebrafish embryonic epidermis, guided by theoretical estimations, reveal a link between epithelial mechanics and cell size, demonstrating that an increase in cell size compromises the tissue fracture strength and compliance. We show that an increase in E-cadherin levels in the proliferation-deficient epidermis restores epidermal compliance but not the fracture strength, which is largely regulated by Ezrin-an apical membrane-cytoskeleton crosslinker. We show that Ezrin fortifies the epithelium in a cell-size-dependent manner by countering non-muscle myosin-II-mediated contractility. This work uncovers the importance of cell size maintenance in regulating the mechanical properties of the epithelium and fostering protection against future mechanical stresses.
摘要：
上皮对机械应力的适应通过分子和组织尺度的变化来促进，包括连接的加强，细胞骨架重组，和细胞增殖介导的组织流变学变化。然而,细胞大小在控制这些特性中的作用仍未得到充分研究。我们在斑马鱼胚胎表皮中的实验，在理论估计的指导下，揭示上皮力学和细胞大小之间的联系，证明细胞大小的增加会损害组织的断裂强度和顺应性。我们表明，在缺乏增殖的表皮中E-cadherin水平的增加可以恢复表皮的顺应性，但不能恢复断裂强度。主要由Ezrin-一种顶膜-细胞骨架交联剂调节。我们证明Ezrin通过对抗非肌肉肌球蛋白II介导的收缩性以细胞大小依赖性的方式强化上皮。这项工作揭示了维持细胞大小在调节上皮的机械性能和促进对未来机械应力的保护方面的重要性。
