Adhesion-regulated junction slippage controls cell intercalation dynamics in an Apposed-Cortex Adhesion Model.
PLoS Comput Biol
Public Library of Science (PLoS)
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Nestor-Bergmann, A., Blanchard, G. B., Hervieux, N., Fletcher, A. G., Étienne, J., & Sanson, B. (2022). Adhesion-regulated junction slippage controls cell intercalation dynamics in an Apposed-Cortex Adhesion Model.. PLoS Comput Biol, 18 (1) https://doi.org/10.1371/journal.pcbi.1009812
Funder: University of Cambridge Herchel Smith Fund
Cell intercalation is a key cell behaviour of morphogenesis and wound healing, where local cell neighbour exchanges can cause dramatic tissue deformations such as body axis extension. Substantial experimental work has identified the key molecular players facilitating intercalation, but there remains a lack of consensus and understanding of their physical roles. Existing biophysical models that represent cell-cell contacts with single edges cannot study cell neighbour exchange as a continuous process, where neighbouring cell cortices must uncouple. Here, we develop an Apposed-Cortex Adhesion Model (ACAM) to understand active cell intercalation behaviours in the context of a 2D epithelial tissue. The junctional actomyosin cortex of every cell is modelled as a continuous viscoelastic rope-loop, explicitly representing cortices facing each other at bicellular junctions and the adhesion molecules that couple them. The model parameters relate directly to the properties of the key subcellular players that drive dynamics, providing a multi-scale understanding of cell behaviours. We show that active cell neighbour exchanges can be driven by purely junctional mechanisms. Active contractility and cortical turnover in a single bicellular junction are sufficient to shrink and remove a junction. Next, a new, orthogonal junction extends passively. The ACAM reveals how the turnover of adhesion molecules regulates tension transmission and junction deformation rates by controlling slippage between apposed cell cortices. The model additionally predicts that rosettes, which form when a vertex becomes common to many cells, are more likely to occur in actively intercalating tissues with strong friction from adhesion molecules.
Research Article, Research and analysis methods, Biology and life sciences, Physical sciences, Engineering and technology
Wellcome Trust (099234/Z/12/Z)
Biotechnology and Biological Sciences Research Council (BB/R000395/1)
Wellcome Trust (207553/Z/17/Z)
External DOI: https://doi.org/10.1371/journal.pcbi.1009812
This record's URL: https://www.repository.cam.ac.uk/handle/1810/334560