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Prof Benoit Ladoux

Institut Jacques Monod

Active behaviors of cellular monolayers

The actomyosin machinery endows cells with contractility at a single cell level. Within a tissue, cells can show either contractile or extensile stresses based on the direction of pushing or pulling forces exerted by their neighbours or on the substrate. In the first part, I will show how these active behaviours and stresses govern fundamental biological processes such as cell extrusion. By modelling the epithelium as an active nematic liquid crystal and measuring mechanical parameters such as strain rates and stresses measurements within cellular monolayers, we show that apoptotic cell extrusion is provoked by singularities in cell alignments in the form of comet-shaped topological defects. The results highlight the importance of active nematic nature of epithelia. However, cellular monolayers display various active behaviors as exemplified by the contractile nature of fibroblasts and the extensile nature of epithelial cells or neural crest cells. In a second part, I will discuss how these two contradictory modes of force generation can coexist. Through a combination of experiments and in silico modeling, we uncover the mechanism behind this switch in behaviour of cell monolayers from extensile to contractile as the weakening of intercellular contacts. We find that this switch in active behaviour also promotes the buildup of tension at the cell-substrate interface through an increase in actin stress fibers and higher traction forces. Such differences in extensility and contractility act to sort cells, thus determining a general mechanism for mechanobiological pattern formation.

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