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20/09/2019 at 11:30
From IJM, Paris (FRA)
will give a seminar entitled :
Studying epithelial tissues as active nematics to understand collective cell migration and cell extrusion
Active nematic materials can be classified into extensile and contractile systems depending on the form of active stresses that they generate. It is well-established that individual epithelial cells exert contractile stresses on their underlying substrate, pulling on the substrate along their elongation axis to move. The new evidence is however surfacing that at the collective level epithelial monolayers manifest extensile behavior, pulling on their sides and pushing along their elongation axes. Using epithelial cells as a model experimental system, we first show that apoptotic cell extrusion is provoked by singularities in cell alignments in the form of comet-shaped topological defects as a signature of the active nematic structure of epithelia. We find a universal correlation between extrusion sites and positions of nematic defects in the cell orientation field in different epithelium types. The results confirm the active nematic nature of epithelia, and demonstrate that defect-induced isotropic stresses are the primary precursors of mechanotransductive responses in cells, including YAP (Yes-associated protein) transcription factor activity11, caspase-3-mediated cell death, and extrusions. Following this analogy with active liquid crystals, we then provide a compelling evidence of extensile activity of epithelial cells and unravel the fundamental mechanobiological mechanism for the switching from contractility at the single cell level to extensility at the collective tissue level. Using molecular perturbation of cell-cell adherence junctions we find that the mechanical state of cell monolayers relies on a cross-talk between cell-matrix and cell-cell adhesions. Contractility emerges at the collective level when the primary adhesion molecule E-cadherin is removed. We further show that this change of behaviour from extensile to contractile stress generation at the collective level is followed by remarkable changes in the mechanical feats of the cells including an increase in the density of stress fibers, enhancing focal adhesions, and even triggering mechanotransductory responses. These results challenge the current consensus that epithelial monolayers are contractile and highlight the role of cell-cell adhesions in mediating the nature of force-transmission between the cells and their ability to form collective patterns of motion.