Cellular segregation in cocultures is driven by differential adhesion and contractility on distinct timescales
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
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.
Details
Original language | English |
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Article number | e2213186120 |
Journal | Proceedings of the National Academy of Sciences of the United States of America : PNAS |
Volume | 120 |
Issue number | 15 |
Publication status | Published - 11 Apr 2023 |
Peer-reviewed | Yes |
External IDs
PubMedCentral | PMC10104523 |
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Scopus | 85151620105 |
ORCID | /0000-0003-0475-3790/work/155291305 |
Keywords
Sustainable Development Goals
Keywords
- Coculture Techniques, Cell Adhesion, Models, Biological, Muscle Contraction