Summary

The intestinal epithelium is a 2D cell monolayer whose function is intrinsically linked to its 3D curved shape. A tight spatio-temporal regulation of proliferation, differentiation and migration takes place in domains with extreme curvature, suggesting an active role of physical forces in intestinal homeostasis. However, due to technical limitations, very little is known about the mechanical processes governing the system. Here we combine intestinal organoids with traction force microscopy to unveil key biomechanical properties of the intestinal epithelium. By means of mechanochemical perturbations of the system, we demonstrate an active role of the intestinal crypt in tissue topography generation. The mechanical landscape uncovered here may have further implications by linking the physical and functional compartmentalization characteristic of the intestine.