Intrinsic cell rheology drives junction maturation.

Autor: Sri-Ranjan K; National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, UK., Sanchez-Alonso JL; National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, UK., Swiatlowska P; National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, UK., Rothery S; National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, UK., Novak P; School of Engineering and Materials Science, Queen Mary University, London, UK., Gerlach S; Institute of Biological Information Processing, IBI-2: Mechanobiology, Julich, Germany., Koeninger D; Institute of Biological Information Processing, IBI-2: Mechanobiology, Julich, Germany., Hoffmann B; Institute of Biological Information Processing, IBI-2: Mechanobiology, Julich, Germany., Merkel R; Institute of Biological Information Processing, IBI-2: Mechanobiology, Julich, Germany., Stevens MM; Department of Materials, Department of Bioengineering and Institute of Biomedical Engineering Imperial College London, London, UK., Sun SX; Department of Mechanical Engineering and Institute of NanoBioTechnology, Johns Hopkins University, Baltimore Maryland, USA., Gorelik J; National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, UK. j.gorelik@imperial.ac.uk., Braga VMM; National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, UK. v.braga@imperial.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Aug 17; Vol. 13 (1), pp. 4832. Date of Electronic Publication: 2022 Aug 17.
DOI: 10.1038/s41467-022-32102-9
Abstrakt: A fundamental property of higher eukaryotes that underpins their evolutionary success is stable cell-cell cohesion. Yet, how intrinsic cell rheology and stiffness contributes to junction stabilization and maturation is poorly understood. We demonstrate that localized modulation of cell rheology governs the transition of a slack, undulated cell-cell contact (weak adhesion) to a mature, straight junction (optimal adhesion). Cell pairs confined on different geometries have heterogeneous elasticity maps and control their own intrinsic rheology co-ordinately. More compliant cell pairs grown on circles have slack contacts, while stiffer triangular cell pairs favour straight junctions with flanking contractile thin bundles. Counter-intuitively, straighter cell-cell contacts have reduced receptor density and less dynamic junctional actin, suggesting an unusual adaptive mechano-response to stabilize cell-cell adhesion. Our modelling informs that slack junctions arise from failure of circular cell pairs to increase their own intrinsic stiffness and resist the pressures from the neighbouring cell. The inability to form a straight junction can be reversed by increasing mechanical stress artificially on stiffer substrates. Our data inform on the minimal intrinsic rheology to generate a mature junction and provide a springboard towards understanding elements governing tissue-level mechanics.
(© 2022. Crown.)
Databáze: MEDLINE
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