Force transmission in epithelia - the impact of next neighbors

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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.