Collective Cell Mechanics of Small-Organoid Morphologies

TL;DR

This paper develops a mechanistic theory using a 3D vertex model to explain the physical origins of diverse small-organoid shapes, emphasizing the roles of surface tension, cell activity, and tissue growth.

Contribution

It introduces a novel 3D surface-tension-based vertex model and an elasticity theory to understand small-organoid morphologies and their physical determinants.

Findings

Branched morphologies depend on junctional activity and topological defects.

Effective elasticity theory estimates apico-basal polarity from cell height modulation.

Physical factors like surface tension and cell rearrangements shape organoid morphology.

Abstract

The study of organoids, artificially grown cell aggregates with the functionality and small-scale anatomy of real organs, is one of the most active areas of research in biology and biophysics, yet the basic physical origins of their different morphologies remain poorly understood. Here we propose a mechanistic theory of small-organoid morphologies. Using a 3D surface-tension-based vertex model, we reproduce the characteristic shapes, ranging from branched and budded structures to invaginated shapes. We find that the formation of branched morphologies relies strongly on junctional activity, enabling temporary aggregations of topological defects in cell packing. To elucidate our numerical results, we develop an effective elasticity theory, which allows one to estimate the apico-basal polarity from the organoid-scale modulation of cell height. Our work provides a generic interpretation of the observed small-organoid morphologies, highlighting the role of physical factors such as the differential surface tension, cell rearrangements, and tissue growth.