Active superelasticity in three-dimensional epithelia of controlled shape

Abstract

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.

Dynamic Mechanics‐Modulated Hydrogels to Regulate the Differentiation of Stem‐Cell Spheroids in Soft Microniches and Modeling of the Nonlinear Behavior

“…In control experiments, YAP was located in the nucleus of the hMSCs when cultured on the tissue culture plates (TCPS) under both culture conditions (Figure S7, Supporting Information). To further understand the mechanism by cyclic mechanical stimuli to stem cell spheroids, the cell encapsulated in LS hydrogels under the dynamic culture condition were treated with (10 × 10 −6 m ) Y27632, an inhibitor of the RhoA‐associated protein kinase (ROCK), which induced nonmuscle myosin II‐mediated contractility and actin filament levels . As previously shown, YAP translocation was also inhibited upon Y27632 daily during the 20 cycles within growth‐media incubation for both hydrogels under the dynamic culture condition (Figure A,D; Figure S8, Supporting Information).…”

Buckling of epithelium growing under spherical confinement

“…Our study adds to the mechanical processes described in vitro to play a role in tissue folding through proliferation, from mesenchymal constriction (20) to constrained heterogeneous growth (21)(22). It also strengthens the concept that unique physical properties of cells are required during morphogenesis, like superelasticity during growth of epithelium domes (23)(24), or liquid to solid phase transition during elongation of the fish embryo (25). Our in vitro findings establish a buckling mechanism that could participate in many epithelium folding events occurring during embryogenesis.…”

Curling of epithelial monolayers reveals coupling between active bending and tissue tension

“…Although each of these mechanisms in isolation can give rise to folding, theoretical and experimental insights suggest that variations of in-plane stresses at the tissue-scale can act in parallel to apical or basal constrictions to define the three-dimensional shape of epithelia (12)(13)(14). Yet, in contrast to the mechanical properties and active forces generated by epithelial monolayers within the plane (11,(15)(16)(17)(18)(19)(20), outof-plane forces and mechanical properties of epithelia (active torques and bending modulus) have not been characterized. Consequently, the relative magnitudes of forces acting inplane and out-of-plane remain unknown, making the contribution of out-of-plane stresses to morphogenesis challenging to assess.…”