标题： 基于钙黏蛋白的细胞间粘附组织上皮细胞-基质牵引力 显示英文标题

标题： Cadherin-Based Intercellular Adhesions Organize Epithelial Cell-Matrix Traction Forces

摘要： 细胞-细胞和细胞-基质粘附在组织功能中起着关键作用。越来越多的证据表明这两种粘附类型之间的交流很重要，但这些相互作用对细胞与细胞外基质（ECM）机械耦合的影响仍知之甚少。在这里，我们结合实验和理论来揭示细胞间粘附如何调节传递到ECM的力。在缺乏钙黏蛋白介导的粘附的情况下，群落中的原代小鼠角质形成细胞似乎独立行动，有显著的牵引力在整个群落中延伸。相反，具有强钙黏蛋白介导的粘附时，紧密群落中的角质形成细胞将牵引力定位在群落边缘。通过基因或抗体介导的钙黏蛋白表达或功能丧失，我们证明钙黏蛋白介导的粘附对于这种机械协同作用是必不可少的。一个最小的物理模型，其中细胞-细胞粘附调节收缩细胞之间的物理粘附性，足以重现随着钙黏蛋白介导粘附强度变化而观察到的牵引力的空间重排。这项工作定义了钙黏蛋白介导的细胞-细胞粘附在协调上皮细胞机械活动中的重要性，并对发育、稳态和疾病过程中上皮组织的机械调控具有重要意义。 显示英文摘要

摘要： Cell--cell and cell-matrix adhesions play essential roles in the function of tissues. There is growing evidence for the importance of crosstalk between these two adhesion types, yet little is known about the impact of these interactions on the mechanical coupling of cells to the extracellular-matrix (ECM). Here, we combine experiment and theory to reveal how intercellular adhesions modulate forces transmitted to the ECM. In the absence of cadherin-based adhesions, primary mouse keratinocytes within a colony appear to act independently, with significant traction forces extending throughout the colony. In contrast, with strong cadherin-based adhesions, keratinocytes in a cohesive colony localize traction forces to the colony periphery. Through genetic or antibody-mediated loss of cadherin expression or function, we show that cadherin-based adhesions are essential for this mechanical cooperativity. A minimal physical model in which cell--cell adhesions modulate the physical cohesion between contractile cells is sufficient to recreate the spatial rearrangement of traction forces observed experimentally with varying strength of cadherin-based adhesions. This work defines the importance of cadherin-based cell--cell adhesions in coordinating mechanical activity of epithelial cells and has implications for the mechanical regulation of epithelial tissues during development, homeostasis, and disease.