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.
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.
School of Physics and Complex and Adaptive Systems Laboratory, University College Dublin, Belfield, Dublin 4, Ireland lukecoburn@gmail.com g.gomez@uq.edu.au.|Institute of Complex Systems and Mathematical Biology, University of Aberdeen, Aberdeen AB24 3FX, United Kingdom.
Luke
L
Coburn
School of Physics and Complex and Adaptive Systems Laboratory, University College Dublin, Belfield, Dublin 4, Ireland.|Center for BioNano Interactions, School of Chemistry and Chemical Biology, University College Dublin, Belfield, Dublin 4, Ireland.
Hender
H
Lopez
Institute for Molecular Bioscience, Division of Cell Biology and Molecular Medicine, University of Queensland, St. Lucia, Brisbane 4072, Australia.
Benjamin J
BJ
Caldwell
Institute for Molecular Bioscience, Division of Cell Biology and Molecular Medicine, University of Queensland, St. Lucia, Brisbane 4072, Australia.
Elliott
E
Moussa
Institute for Molecular Bioscience, Division of Cell Biology and Molecular Medicine, University of Queensland, St. Lucia, Brisbane 4072, Australia.
Chloe
C
Yap
Institute for Molecular Bioscience, Division of Cell Biology and Molecular Medicine, University of Queensland, St. Lucia, Brisbane 4072, Australia.
Rashmi
R
Priya
School of Mathematics and Physics, University of Queensland, St. Lucia, Brisbane 4072, Australia.
Adrian
A
Noppe
School of Mathematics and Physics, University of Queensland, St. Lucia, Brisbane 4072, Australia.
Anthony P
AP
Roberts
School of Physics and Complex and Adaptive Systems Laboratory, University College Dublin, Belfield, Dublin 4, Ireland.
Vladimir
V
Lobaskin
Institute for Molecular Bioscience, Division of Cell Biology and Molecular Medicine, University of Queensland, St. Lucia, Brisbane 4072, Australia.
Alpha S
AS
Yap
Institute for Molecular Bioscience, Division of Cell Biology and Molecular Medicine, University of Queensland, St. Lucia, Brisbane 4072, Australia.|School of Mathematics and Physics, University of Queensland, St. Lucia, Brisbane 4072, Australia.
Zoltan
Z
Neufeld
Institute for Molecular Bioscience, Division of Cell Biology and Molecular Medicine, University of Queensland, St. Lucia, Brisbane 4072, Australia lukecoburn@gmail.com g.gomez@uq.edu.au.
Guillermo A
GA
Gomez
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D022081:Cell Surface Extensions / Q000378:metabolism / Q000502:physiology; D003198:Computer Simulation / Q000706:statistics & numerical data; D003260:Contact Inhibition / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D004848:Epithelium; D006801:Humans; D007365:Intercellular Junctions; D008124:Locomotion; D008954:Models, Biological; D020239:Receptor Cross-Talk