Contact inhibition of locomotion and mechanical cross-talk between cell-cell and cell-substrate adhesion determine the pattern of junctional tension in epithelial cell aggregates
Authors list
Luke Coburn Hender Lopez Benjamin J Caldwell Elliott Moussa Chloe Yap Rashmi Priya Adrian Noppe Anthony P Roberts Vladimir Lobaskin Alpha S Yap Zoltan Neufeld Guillermo A GomezAbstract
We used a computational approach to analyze the biomechanics of epithelial cell aggregates-islands, stripes, or entire monolayers-that combines both vertex and contact-inhibition-of-locomotion models to include cell-cell and cell-substrate adhesion. Examination of the distribution of cell protrusions (adhesion to the substrate) in the model predicted high-order profiles of cell organization that agree with those previously seen experimentally. Cells acquired an asymmetric distribution of basal protrusions, traction forces, and apical aspect ratios that decreased when moving from the edge to the island center. Our in silico analysis also showed that tension on cell-cell junctions and apical stress is not homogeneous across the island. Instead, these parameters are higher at the island center and scale up with island size, which we confirmed experimentally using laser ablation assays and immunofluorescence. Without formally being a three-dimensional model, our approach has the minimal elements necessary to reproduce the distribution of cellular forces and mechanical cross-talk, as well as the distribution of principal stress in cells within epithelial cell aggregates. By making experimentally testable predictions, our approach can aid in mechanical analysis of epithelial tissues, especially when local changes in cell-cell and/or cell-substrate adhesion drive collective cell behavior.
Journal details
Journal Molecular Biology of the Cell
Volume 27
Issue number 22
Pages 3436-3448
Available online
Publication date
Full text links
Publisher website (DOI) 10.1091/mbc.E16-04-0226
Europe PubMed Central 27605701
Pubmed 27605701
Keywords
Type of publication