Control of collective cell dynamics by adhesion, tension and fracking
Xavier Trepat (ICREA @ Institute for Bioengineering of Catalonia (IBEC), Barcelona)
A broad range of biological processes such as morphogenesis, tissue regeneration, and cancer invasion depend on the collective dynamics of epithelial cells. Such dynamics are determined by an exquisite balance between intercellular adhesion, cytoskeletal tension, and intracellular pressure. To study this balance in a fully quantitative manner I will present new techniques to map physical forces between and within cells. Using these techniques we studied how cellular forces are regulated and transmitted by the proteins that comprise intercellular adhesion complexes. To do so, we perturbed the main molecular players of the intercellular adhesome using RNAi and studied how these perturbations impact physical forces and cellular velocities in epithelial cell collectives. We found that perturbations targeting adherens junctions, but also tight junctions, gap junctions, and desmosomes have a significant impact on cell velocities, cell deformations, cell-matrix traction forces, and cell-cell forces. We developed a cross-validation analysis to show that concentrations of cell-cell adhesion proteins are significant predictors of cell-cell forces. Finally, I will discuss the determinants of epithelial integrity in the presence of stretching and transepithelial pressure.