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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Mark Skamrahl - , University Medical Center Göttingen (Author)
  • Justus Schünemann - , University Medical Center Göttingen (Author)
  • Markus Mukenhirn - , Chair of Biophysics, Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Hongtao Pang - , University Medical Center Göttingen (Author)
  • Jannis Gottwald - , University Medical Center Göttingen (Author)
  • Marcel Jipp - , University Medical Center Göttingen (Author)
  • Maximilian Ferle - , University Medical Center Göttingen (Author)
  • Angela Rübeling - , University Medical Center Göttingen (Author)
  • Tabea A Oswald - , University Medical Center Göttingen (Author)
  • Alf Honigmann - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Andreas Janshoff - , University Medical Center Göttingen (Author)

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 languageEnglish
Article numbere2213186120
JournalProceedings of the National Academy of Sciences of the United States of America : PNAS
Volume120
Issue number15
Publication statusPublished - 11 Apr 2023
Peer-reviewedYes

External IDs

PubMedCentral PMC10104523
Scopus 85151620105
ORCID /0000-0003-0475-3790/work/155291305

Keywords

Sustainable Development Goals

Keywords

  • Coculture Techniques, Cell Adhesion, Models, Biological, Muscle Contraction