Force transmission in epithelia - the impact of next neighbors

上皮细胞中的力传递 - 最近邻居的影响

• 批准号: 273723851
• 负责人: Professor Dr. Andreas Janshoff
• 金额: --
• 依托单位: Institut für Physikalische Chemie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/273723851?language=en
• 关键词: Force; transmission; epithelia; impact; next

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.

上皮细胞层中的力传递很大程度上是由细胞内连接到收缩细胞骨架的细胞间连接介导的。组织经历持续重塑，需要相邻细胞之间的紧密平衡的机械力，这主要由钙粘蛋白介导的细胞间连接来控制。细胞之间的机械耦合已被报道用于多种多细胞过程，例如上皮间质转化、胚胎发生和癌症进展。该项目的目标是测量力具体而言，我们将实现两种方法：(i) 允许使用软可变形壁测量细胞间相互作用力；(ii) ) ) 通过映射嵌入细胞层中的可调谐微柱的偏转，可以了解细胞单层中的动态应力模式。有了这些设备，并在皮质和膜张力的力体积映射的帮助下我们计划使用原子力显微镜检查针对粘附连接、紧密连接和桥粒中不同蛋白质的细胞骨架药物和基因沉默对应力模式和相互作用力的影响，从而实现的主要目标是阐明。全局和局部扰动对细胞反应的合作（相关长度）的影响，这对细胞在更大范围内的机械通信方式具有深远的影响。