Force transmission in epithelia - the impact of next neighbors

上皮细胞层中的力传递主要是由细胞间连接的存在介导的，该连接在细胞内侧上连接到收缩性细胞骨架。组织经历连续的重塑，需要紧密平衡的机械力之间的相邻细胞主要由钙粘蛋白介导的细胞连接控制。细胞之间的机械耦合的重要性已被报道的各种多细胞过程，如上皮细胞间质转化，胚胎发育和癌症的progress.The项目的目标是测量力传递和mechanictransductionofcell-cell接触的上下文中，汇合的上皮单层受到局部和全局的外部扰动。具体地说，我们将实现两种方法，（i）允许使用软变形壁测量细胞-细胞相互作用力，（ii）通过映射嵌入细胞层中的可调微柱的偏转来获得细胞单层中的动态应力模式。有了这些设备，并通过使用原子力显微镜的皮质和膜张力的力体积映射来辅助，我们计划研究细胞骨架药物和靶向位于粘附连接、紧密连接和桥粒中的不同蛋白质的基因沉默对应力模式和相互作用力的影响。由此达到的主要目标是阐明整体和局部扰动对细胞反应的协同性（相关长度）的影响。这对细胞在更大尺度上的机械通信方式具有深远的影响。

Force transmission in epithelial cell layers is largely mediated by the presence of intercellular junctions connected on the innercellular side to the contractile cytoskeleton. Tissues undergo continuous remodeling that requires tightly balanced mechanical forces between adjacent cells mainly controlled by cadherin-mediated cell–cell junctions. The importance of mechanical coupling between cells has been reported for a variety of multi-cellular processes, such as epithelial-to-mesenchymal transition, embryogenesis and cancer progression.The goal of the project is to measure the force transmission and mechanotransduction of cell-cell contacts in the context of confluent epithelial monolayers subject to local and global external perturbations. Concretely, we will realize two methods that (i) permit to measure cell-cell interaction forces using soft deformable walls and that (ii) gives access to the dynamic stress pattern in a cell monolayer by mapping the deflection of tunable micropillars embedded in the cell layer.With these devices in hand and assisted by force volume mapping of the cortical and membrane tension using an atomic force microscope, we plan to examine the impact of cytoskeletal drugs and gene silencing targeting the different proteins located in adherens junctions, tight junctions and desmosomes on the stress pattern and interaction forces. The primary goal that thereby comes into reach is the elucidation of the impact of global and local perturbations on the cooperativity (correlation length) of the cellular response. This has far reaching implications of the way cells communicate mechanically on larger scales.