Cellular segregation in cocultures is driven by differential adhesion and contractility on distinct timescales.

First Authors Mark Skamrahl
Authors Mark Skamrahl, Justus Schünemann, Markus Mukenhirn, Hongtao Pang, Jannis Gottwald, Marcel Jipp, Maximilian Ferle, Angela Rübeling, Tabea A Oswald, Alf Honigmann, Andreas Janshoff
Corresponding Authors Andreas Janshoff
Last Authors Andreas Janshoff
Journal Name Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U.S.A.)
Volume 120
Issue 15
Article Number e2213186120
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Print Publication Date 2023-04-11
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Abstract Cellular sorting and pattern formation are crucial for many biological processes such as development, tissue regeneration, and cancer progression. Prominent physical driving forces for cellular sorting are differential adhesion and contractility. Here, we studied the segregation of epithelial cocultures containing highly contractile, ZO1/2-depleted MDCKII cells (dKD) and their wild-type (WT) counterparts using multiple quantitative, high-throughput methods to monitor their dynamical and mechanical properties. We observe a time-dependent segregation process governed mainly by differential contractility on short (<5 h) and differential adhesion on long (>5 h) timescales. The overly contractile dKD cells exert strong lateral forces on their WT neighbors, thereby apically depleting their surface area. Concomitantly, the tight junction-depleted, contractile cells exhibit weaker cell-cell adhesion and lower traction force. Drug-induced contractility reduction and partial calcium depletion delay the initial segregation but cease to change the final demixed state, rendering differential adhesion the dominant segregation force at longer timescales. This well-controlled model system shows how cell sorting is accomplished through a complex interplay between differential adhesion and contractility and can be explained largely by generic physical driving forces.
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DOI 10.1073/pnas.2213186120
PubMed ID 37011207
WebOfScience Link WOS:001025193500003
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Created By thuem
Added Date 2023-04-11
Last Edited By thuem
Last Edited Date 2023-08-10 14:50:58.996
Library ID 8521
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