Active wetting of epithelial tissues

Abstract

Development, regeneration and cancer involve drastic transitions in tissue morphology. In analogy with the behavior of inert fluids, some of these transitions have been interpreted as wetting transitions. The validity and scope of this analogy are unclear, however, because the active cellular forces that drive tissue wetting have been neither measured nor theoretically accounted for. Here we show that the transition between two-dimensional epithelial monolayers and three-dimensional spheroidal aggregates can be understood as an active wetting transition whose physics differs fundamentally from that of passive wetting phenomena. By combining an active polar fluid model with measurements of physical forces as a function of tissue size, contractility, cell-cell and cell-substrate adhesion, and substrate stiffness, we show that the wetting transition results from the competition between traction forces and contractile intercellular stresses. This competition defines a new intrinsic lengthscale that gives rise to a critical size for the wetting transition in tissues, a striking feature that has no counterpart in classical wetting. Finally, we show that active shape fluctuations are dynamically amplified during tissue dewetting. Overall, we conclude that tissue spreading constitutes a prominent example of active wetting — a novel physical scenario that may explain morphological transitions during tissue morphogenesis and tumor progression.

Size-dependent patterns of cell proliferation and migration in freely-expanding epithelia

“…Due to the complexity of collective behaviors, much effort has gone towards reductionist assays that restrict degrees of freedom and ensemble size to simplify analysis and interpretation. One powerful approach is to confine a tissue within predefined boundaries using micropatterning to create adhesive and non-adhesive regions (6)(7)(8)(9)(10)(11). Such confinement mimics certain in vivo contexts such as constrained tumors as well as aspects of compartmentalization during morphogenesis (12).…”

Tissue rheology in embryonic organization

“…By studying cell behaviour of 3D spheroidal aggregates placed on a solid and adhesive substrate, it was observed that over time the 3D cluster starts to spread on the substrate forming a 2D layer with cells individually leaving the cluster, a hallmark of EMT (Douezan et al, 2011). The reverse transition, also called de-wetting, was found in epithelial 2D monolayers, where increasing the level of E-cadherin triggers a sudden morphological transition into 3D clusters (Pérez-González et al, 2019). The reverse transition, also called de-wetting, was found in epithelial 2D monolayers, where increasing the level of E-cadherin triggers a sudden morphological transition into 3D clusters (Pérez-González et al, 2019).…”

“…This process was further described by a wetting behaviour depending on the levels of E-cadherin, where highly cohesive aggregates are in a liquid state, while in weakly cohesive aggregates, cells escape and undergo a liquid-to-gas transition (Douezan et al, 2011) (Glossary). Theoretical modelling suggested that this de-wetting transition is triggered at a critical point of cell contractility regulated by the E-cadherin levels, and cellsubstrate adhesion energy regulated by substrate ligand density and monolayer size (Pérez-González et al, 2019). Theoretical modelling suggested that this de-wetting transition is triggered at a critical point of cell contractility regulated by the E-cadherin levels, and cellsubstrate adhesion energy regulated by substrate ligand density and monolayer size (Pérez-González et al, 2019).…”

“…The reverse transition, also called de-wetting, was found in epithelial 2D monolayers, where increasing the level of E-cadherin triggers a sudden morphological transition into 3D clusters (Pérez-González et al, 2019). Theoretical modelling suggested that this de-wetting transition is triggered at a critical point of cell contractility regulated by the E-cadherin levels, and cellsubstrate adhesion energy regulated by substrate ligand density and monolayer size (Pérez-González et al, 2019). Understanding tissue spreading as a phase transition-mediated process may also be important for understanding embryo morphogenesis.…”

Compaction dynamics during progenitor cell self-assembly reveal granular mechanics

“…By studying their deformation dynamics, the relative viscosity of spreading cell aggregates could be deduced (11). On adhesive substrates, it has been shown that shape fluctuations caused by active tractions may induce morphological instabilities that introduce a colony size dependency to the wetting transition (13). On soft and/or weakly adhesive substrates, cells are unable to generate significant substrate traction forces.…”