Shape stabilization in budding intestinal organoids by geometrical ratcheting

Abstract

The intestinal epithelium in vertebrates has a characteristic arrangement of protruding villi and receding crypts, which are generated and stabilized by selforganized cell forces. Intestinal organoids recapitulate this development and can be used to shed light on the underlying mechanical processes. Here we combine advanced image processing and the bubbly vertex model for epithelial cell shape to achieve a fully three-dimensional reconstruction of cell shapes, forces and tissue geometries during the development of mouse intestinal organoids. We show that the transition from spherical to budded morphologies is caused by a global increase in tension at the inner side and a decrease in luminal pressure, which however are not maintained after budding, suggesting ratchet-like non-reversibility. Through computer simulations of a vertex model for growing tissue with T1-transitions and comparison with the experimental data, we show that this ratchet is likely of geometrical origin. We further find that the system is mechanically stabilized on the outer side by increases in line tensions and reorganization of the actomyosin network, stabilizing a polygonal organization that also seems to enforce the geometrical ratchet. Our approach demonstrates how one can achieve a complete mechanical analysis of a complex tissue-like system.