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

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Mark Skamrahl - , Universitätsmedizin Göttingen (Autor:in)
  • Hongtao Pang - , Universitätsmedizin Göttingen (Autor:in)
  • Maximilian Ferle - , Universitätsmedizin Göttingen (Autor:in)
  • Jannis Gottwald - , Universitätsmedizin Göttingen (Autor:in)
  • Angela Rübeling - , Universitätsmedizin Göttingen (Autor:in)
  • Riccardo Maraspini - , Professur für Biophysik, Max Planck Institute of Molecular Cell Biology and Genetics (Autor:in)
  • Alf Honigmann - , Max Planck Institute of Molecular Cell Biology and Genetics (Autor:in)
  • Tabea A Oswald - , Universitätsmedizin Göttingen (Autor:in)
  • Andreas Janshoff - , Universitätsmedizin Göttingen (Autor:in)

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

OriginalspracheEnglisch
Seiten (von - bis)e2100478
FachzeitschriftAdvanced Science
Jahrgang8
Ausgabenummer19
PublikationsstatusVeröffentlicht - Okt. 2021
Peer-Review-StatusJa

Externe IDs

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

Schlagworte

Schlagwörter

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