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

Autor: Skamrahl M; Institute of Physical Chemistry, University of Göttingen, Tammannstr. 6, Göttingen, 37077, Germany., Pang H; Institute of Physical Chemistry, University of Göttingen, Tammannstr. 6, Göttingen, 37077, Germany., Ferle M; Institute of Physical Chemistry, University of Göttingen, Tammannstr. 6, Göttingen, 37077, Germany., Gottwald J; Institute of Physical Chemistry, University of Göttingen, Tammannstr. 6, Göttingen, 37077, Germany., Rübeling A; Institute of Organic and Biomolecular Chemistry, University of Göttingen, Tammannstr. 2, Göttingen, 37077, Germany., Maraspini R; Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstraße 108, Dresden, 01307, Germany., Honigmann A; Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstraße 108, Dresden, 01307, Germany., Oswald TA; Institute of Organic and Biomolecular Chemistry, University of Göttingen, Tammannstr. 2, Göttingen, 37077, Germany., Janshoff A; Institute of Physical Chemistry, University of Göttingen, Tammannstr. 6, Göttingen, 37077, Germany.
Jazyk: angličtina
Zdroj: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2021 Oct; Vol. 8 (19), pp. e2100478. Date of Electronic Publication: 2021 Aug 12.
DOI: 10.1002/advs.202100478
Abstrakt: 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.
(© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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