Active wetting of epithelial tissues.

Abstract

Development, regeneration and cancer involve changes in cell mechanical properties that lead to drastic transitions in tissue geometry and dimensionality. Given the fluid nature of living tissues, these transitions have been experimentally studied and theoretically modelled in terms of the physics of wetting phenomena, which describes how a fluid droplet spreads on a solid surface. However, physical forces, the effective determinants of tissue spreading, have never been measured in the context of tissue wetting. Here we perform a systematic study of tissue mechanics during epithelial wetting/dewetting. We induce a progressive expression of E‐cadherin in a confined monolayer of MDA‐MB‐231 cells and, simultaneously, we measure tissue forces using Traction Force Microscopy and Monolayer Stress Microscopy. The gradual formation of intercellular junctions produces a continuous increase in tissue contractility (pMLC), triggering a two‐fold increase in tissue forces that ends up in a spontaneous wetting‐dewetting transition. To understand how this transition arises from tissue active properties, we develop a wetting model based on active gels theory. Combining theory and experiments, we find that wetting‐dewetting transition results from a competition between contractility and traction forces, which introduces a new length scale, defining a critical size for tissue wetting. Strikingly, this implies that the critical tissue contractility driving the transition is dependent on tissue size, a phenomenon that has no counterpart in passive wetting/dewetting physics. Furthermore, we find that the critical tractions, which depend linearly on substrate ligand density, are the mechanical threshold for tissue spreading. Finally, we show that long‐wavelength morphological instabilities in our fluid interface, together with active fluctuations, explain tissue shape dynamics during dewetting. We conclude that tissue spreading can be understood as an active wetting transition of a viscous polar fluid.