Active superelasticity in three-dimensional epithelia of controlled shape

Fundamental biological processes are carried out by curved epithelial sheets that enclose a pressurized lumen. How these sheets develop and withstand three-dimensional deformations has remained unclear. Here we combine measurements of epithelial tension and shape with theoretical modelling to 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 strains in the tissue are accommodated by highly heterogeneous strains at a cellular level, in seeming contradiction to the measured tensional uniformity. This phenomenon is reminiscent of superelasticity, a behaviour that is generally attributed to microscopic material instabilities in metal alloys. We show that in epithelial cells this instability is triggered by a stretch-induced dilution of the actin cortex, and is rescued by the intermediate filament network. Our study reveals a type of mechanical behaviour—which we term active superelasticity—that enables epithelial sheets to sustain extreme stretching under constant tension.Peer ReviewedPostprint (author's final draft

Mapping mechanical stress in curved epithelia of designed size and shape

We thank C. Pérez-González, N. Castro, and all of the members of the Roca-Cusachs, Arroyo, and Trepat laboratories for their discussions and support. This work was supported by: Generalitat de Catalunya (Agaur, SGR-2021-01425 to X.T., SGR-2021-00523 to R.S., the CERCA Programme, and “ICREA Academia” award to M.A. and P.R-C.); Spanish Ministry for Science and Innovation MICCINN/FEDER (PID2021- 128635NB-I00, MCIN/AEI/ 10.13039/501100011033 and “ERDF-EU A way of making Europe” to X.T., PID2019-110949GB-I00 to M.A., PID2019- 110298GB-I00 to P.R.-C., PID2021-128674OB-I00, RTI2018-101256-J-I00, and RYC2019-026721-I to R.S.); European Research Council (Adv883739 to X.T., CoG-681434 to M.A.); Fundació la Marató de TV3 (project 201903-30-31-32 to X.T.); Deutsche Forschungsgemeinschaft (DFG GO3403/1-1 to T.G.); IBEC, IRB, and CIMNE are recipients of a Severo Ochoa Award of Excellence from the MINECO; European Commission (H2020-FETPROACT-01-2016-731957 to P.R-C.); La Caixa Foundation (LCF/PR/HR20/52400004 and ID 100010434 under the agreement LCF/ PR/HR20/52400004 to P.R-C. and X.T.). R.S. is a Serra Húnter fellow.The function of organs such as lungs, kidneys and mammary glands relies on the three-dimensional geometry of their epithelium. To adopt shapes such as spheres, tubes and ellipsoids, epithelia generate mechanical stresses that are generally unknown. Here we engineer curved epithelial monolayers of controlled size and shape and map their state of stress. We design pressurized epithelia with circular, rectangular and ellipsoidal footprints. We develop a computational method, called curved monolayer stress microscopy, to map the stress tensor in these epithelia. This method establishes a correspondence between epithelial shape and mechanical stress without assumptions of material properties. In epithelia with spherical geometry we show that stress weakly increases with areal strain in a size-independent manner. In epithelia with rectangular and ellipsoidal cross-section we find pronounced stress anisotropies that impact cell alignment. Our approach enables a systematic study of how geometry and stress influence epithelial fate and function in three-dimensions.Peer ReviewedPostprint (published version

Active superelasticity in three-dimensional epithelia of controlled shape

Fundamental biological processes are carried out by curved epithelial sheets that enclose a pressurized lumen. How these sheets develop and withstand three-dimensional deformations has remained unclear. Here we combine measurements of epithelial tension and shape with theoretical modelling to 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 strains in the tissue are accommodated by highly heterogeneous strains at a cellular level, in seeming contradiction to the measured tensional uniformity. This phenomenon is reminiscent of superelasticity, a behaviour that is generally attributed to microscopic material instabilities in metal alloys. We show that in epithelial cells this instability is triggered by a stretch-induced dilution of the actin cortex, and is rescued by the intermediate filament network. Our study reveals a type of mechanical behaviour—which we term active superelasticity—that enables epithelial sheets to sustain extreme stretching under constant tension.Peer Reviewe