Abstract
Epithelial cell extrusion is employed in maintaining a healthy epithelium. It remains unclear how environmental conditions specific to various epithelial tissues, such as geometry and fluid osmolarity, affect cell extrusions. We found that, over curved surfaces, epithelial monolayers exhibited higher extrusion rates in concave regions than convex ones. This difference, and overall extrusions, decreased when osmotically induced basal hydraulic stress was reduced by increasing media osmolarity or by culturing monolayers on hydrogels. Mechanistically, basal fluid accumulation antagonized cell-substrate adhesions and the subsequent FAK-Akt survival pathway, leading to apoptotic cell death. Convex surfaces induced cellular forces that acted against osmosis, thereby promoting adhesions and lowering apoptosis. This effect was reversed in concave regions, and together, resulted in the curvature induced spatial bias in cell extrusions.
One-Sentence Summary Curvature induces forces in cell-sheets that act against/with osmosis to reduce/elevate fluid stress driven cell extrusions.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
1. Amended abstract and structure of text to improve readability. 2. Includes 25% PBS treatment as a comparison to 25% water treatment (fig. 2). 3. Included extra verification that reducing osmolarity by reducing 65 mOsm does not directly kill cells (new movie S14). 4. Corrected typos and errors in text. 5. Included comprehensive tables of results and statistical analysis. 6. Improved diagrams for better clarity. 7. Added extra references.
