PT  - JOURNAL ARTICLE
AU  - Alexis J. Haas
AU  - Ceniz Zihni
AU  - Susanne M. Krug
AU  - Riccardo Maraspini
AU  - Tetsuhisa Otani
AU  - Mikio Furuse
AU  - Alf Honigmann
AU  - Maria Balda
AU  - Karl Matter
TI  - Reciprocal regulation between cell mechanics and ZO-1 guides tight junction assembly and epithelial morphogenesis
AID  - 10.1101/2022.07.17.500023
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.07.17.500023
4099  - http://biorxiv.org/content/early/2022/07/18/2022.07.17.500023.short
4100  - http://biorxiv.org/content/early/2022/07/18/2022.07.17.500023.full
AB  - Formation and maintenance of tissue barriers require the coordination of cell mechanics and cell-cell junction assembly. Here, we combined methods to modulate ECM stiffness and to measure mechanical forces on adhesion complexes to investigate how tight junctions regulate cell mechanics and epithelial morphogenesis. We found that depletion of the tight junction adaptor ZO-1 regulates cytoskeletal tension at cell-matrix and cell-cell interfaces in an ECM stiffness-regulated manner, possibly via differential organisation of the actin cytoskeleton. ZO-1 depletion inhibited junction assembly and disrupted morphogenesis in an ECM stiffness-dependent manner. Both processes were rescued by inhibition of cell contractility. Although ZO-1-deficient cells could assemble functional barriers at low tension, their tight junctions remained corrupted with strongly reduced and discontinuous recruitment of junctional components. Our results thus reveal that reciprocal regulation between ZO-1 and cell mechanics controls tight junction assembly and epithelial morphogenesis, and that tension-independent roles of ZO-1 control proper junction organisation.Competing Interest StatementThe authors have declared no competing interest.