Tight Junction ZO Proteins Maintain Tissue Fluidity, Ensuring Efficient Collective Cell Migration

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

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

Abstract

Tight junctions (TJs) are essential components of epithelial tissues connecting neighboring cells to provide protective barriers. While their general function to seal compartments is well understood, their role in collective cell migration is largely unexplored. Here, the importance of the TJ zonula occludens (ZO) proteins ZO1 and ZO2 for epithelial migration is investigated employing video microscopy in conjunction with velocimetry, segmentation, cell tracking, and atomic force microscopy/spectroscopy. The results indicate that ZO proteins are necessary for fast and coherent migration. In particular, ZO1 and 2 loss (dKD) induces actomyosin remodeling away from the central cortex towards the periphery of individual cells, resulting in altered viscoelastic properties. A tug-of-war emerges between two subpopulations of cells with distinct morphological and mechanical properties: 1) smaller and highly contractile cells with an outward bulging apical membrane, and 2) larger, flattened cells, which, due to tensile stress, display a higher proliferation rate. In response, the cell density increases, leading to crowding-induced jamming and more small cells over time. Co-cultures comprising wildtype and dKD cells migrate inefficiently due to phase separation based on differences in contractility rather than differential adhesion. This study shows that ZO proteins are necessary for efficient collective cell migration by maintaining tissue fluidity and controlling proliferation.

Details

Original languageEnglish
Pages (from-to)e2100478
JournalAdvanced Science
Volume8
Issue number19
Publication statusPublished - Oct 2021
Peer-reviewedYes

External IDs

PubMedCentral PMC8498871
Scopus 85112223471
ORCID /0000-0003-0475-3790/work/155291289

Keywords

Keywords

  • Animals, Cell Line, Cell Movement/physiology, Dogs, Epithelial Cells/chemistry, Epithelium/chemistry, Tight Junctions/chemistry, Zonula Occludens Proteins/chemistry