Fundamental biological processes are carried out by curved epithelial sheets enclosing a pressurized lumen. How these sheets develop and withstand three-dimensional deformations has remained unclear. By combining measurements of epithelial tension and shape with theoretical modeling, here we show that epithelial sheets are active superelastic materials. We produce arrays of epithelial domes with controlled geometry. Quantification of luminal pressure and epithelial tension reveals a tensional plateau over several-fold areal strains. These extreme tissue strains are accommodated by highly heterogeneous cellular strains, in seeming contradiction with the measured tensional uniformity. This phenomenology is reminiscent of superelasticity, a behavior generally attributed to microscopic material instabilities in metal alloys. We show that this instability is triggered in epithelial cells by a stretch-induced dilution of the actin cortex and rescued by the intermediate filament network. Our study unveils a new type of mechanical behavior -active superelasticity- that enables epithelial sheets to sustain extreme stretching under constant tension.

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.

Living tissues are active multifunctional materials capable of generating, sensing, withstanding and responding to mechanical stress. These capabilities enable tissues to adopt complex shapes during development, to sustain those shapes during homeostasis, and to restore them during healing and regeneration. Abnormal stress is associated with a broad range of pathologies, including developmental defects, inflammatory diseases, tumor growth and metastasis. Here we review techniques that measure mechanical stress in living tissues with cellular and subcellular resolution. We begin with 2D techniques to map stress in cultured cell monolayers, which provide the highest resolution and accessibility. These techniques include 2D traction microscopy, micro-pillar arrays, monolayer stress microscopy, and monolayer stretching between flexible cantilevers. We next focus on 3D traction microscopy and the micro-bulge test, which enable mapping forces in tissues cultured in 3D. Finally, we review techniques to measure stress in vivo, including servo-null methods for measuring luminal pressure, deformable inclusions, FRET sensors, laser ablation and computational methods for force inference. Whereas these techniques remain far from becoming everyday tools in biomedical laboratories, their rapid development is fostering key advances in the way we understand the role of mechanics in morphogenesis, homeostasis and disease.