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 epithelial shells which resemble small-organoid morphologies. Using a 3D surface tension-based vertex model, we reproduce the characteristic shapes from branched and budded to invaginated structures. 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 tissue-scale modulation of cell height. Our work provides a generic interpretation of the observed epithelial shell morphologies, highlighting the role of physical factors such as differential surface tension, cell rearrangements, and tissue growth.
Highlights
The study of organoids, artificially grown cell aggregates with the functionality and smallscale 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
We explore the formation of inplane cell arrangements and find that topological defects in cell packing induced by active rearrangements can act as seeds for branching morphogenesis, leading to out-of-equilibrium branched shapes
These results reveal the generic mechanisms of morphogenesis of small epithelial shells of identical cells
Summary
The study of organoids, artificially grown cell aggregates with the functionality and smallscale 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. Our work provides a generic interpretation of the observed epithelial shell morphologies, highlighting the role of physical factors such as differential surface tension, cell rearrangements, and tissue growth. Together with results addressing transformations of epithelial shells[12], these insights demonstrate that many features of the observed organoid shapes can be interpreted using physical models based on mechanisms arising from the underlying cell- and tissue-level biological processes. We enhance this perspective by analyzing a surface tension-based vertex model of single-cell-thick epithelial shells. These results reveal the generic mechanisms of morphogenesis of small epithelial shells of identical cells
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