Intercellular adhesion boots collective cell migration through elevated membrane tension

Abstract In multicellular systems, the migration pattern of individual cells critically relies on the interactions with neighboring cells. Depending on the strength of these interactions, cells either move as a collective, as observed during morphogenesis and wound healing, or migrate individually,...

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Main Authors: Brent M. Bijonowski, Jongkwon Park, Martin Bergert, Christina Teubert, Alba Diz-Muñoz, Milos Galic, Seraphine V. Wegner
Format: Article
Language:English
Published: Nature Portfolio 2025-02-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-56941-4
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author Brent M. Bijonowski
Jongkwon Park
Martin Bergert
Christina Teubert
Alba Diz-Muñoz
Milos Galic
Seraphine V. Wegner
author_facet Brent M. Bijonowski
Jongkwon Park
Martin Bergert
Christina Teubert
Alba Diz-Muñoz
Milos Galic
Seraphine V. Wegner
author_sort Brent M. Bijonowski
collection DOAJ
description Abstract In multicellular systems, the migration pattern of individual cells critically relies on the interactions with neighboring cells. Depending on the strength of these interactions, cells either move as a collective, as observed during morphogenesis and wound healing, or migrate individually, as it is the case for immune cells and fibroblasts. Mediators of cell-cell adhesions, such as cadherins coordinate collective dynamics by linking the cytoskeleton of neighboring cells. However, whether intercellular binding alone triggers signals that originate from within the plasma membrane itself, remains unclear. Here, we address this question through artificial photoswitchable cell-cell adhesions that selectively connect adjacent plasma membranes without linking directly to cytoskeletal elements. We find that these intercellular adhesions are sufficient to achieve collective cell migration. Linking adjacent cells increases membrane tension, which activates the enzyme phospholipase D2. The resulting increase in phosphatidic acid, in turn, stimulates the mammalian target of rapamycin, a known actuator of collective cell migration. Collectively, these findings introduce a membrane-based signaling axis as promotor of collective cell dynamics, which is independent of the direct coupling of cell-cell adhesions to the cytoskeleton.
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spelling doaj-art-ed2faa25d62f484193409ad56d7dbb422025-08-20T02:48:27ZengNature PortfolioNature Communications2041-17232025-02-0116111410.1038/s41467-025-56941-4Intercellular adhesion boots collective cell migration through elevated membrane tensionBrent M. Bijonowski0Jongkwon Park1Martin Bergert2Christina Teubert3Alba Diz-Muñoz4Milos Galic5Seraphine V. Wegner6Institute of Physiological Chemistry and Pathobiochemistry, University of MünsterInstitute of Physiological Chemistry and Pathobiochemistry, University of MünsterCell Biology and Biophysics Unit, European Molecular Biology LaboratoryInstitute of Medical Physics and Biophysics, University of MünsterCell Biology and Biophysics Unit, European Molecular Biology LaboratoryInstitute of Medical Physics and Biophysics, University of MünsterInstitute of Physiological Chemistry and Pathobiochemistry, University of MünsterAbstract In multicellular systems, the migration pattern of individual cells critically relies on the interactions with neighboring cells. Depending on the strength of these interactions, cells either move as a collective, as observed during morphogenesis and wound healing, or migrate individually, as it is the case for immune cells and fibroblasts. Mediators of cell-cell adhesions, such as cadherins coordinate collective dynamics by linking the cytoskeleton of neighboring cells. However, whether intercellular binding alone triggers signals that originate from within the plasma membrane itself, remains unclear. Here, we address this question through artificial photoswitchable cell-cell adhesions that selectively connect adjacent plasma membranes without linking directly to cytoskeletal elements. We find that these intercellular adhesions are sufficient to achieve collective cell migration. Linking adjacent cells increases membrane tension, which activates the enzyme phospholipase D2. The resulting increase in phosphatidic acid, in turn, stimulates the mammalian target of rapamycin, a known actuator of collective cell migration. Collectively, these findings introduce a membrane-based signaling axis as promotor of collective cell dynamics, which is independent of the direct coupling of cell-cell adhesions to the cytoskeleton.https://doi.org/10.1038/s41467-025-56941-4
spellingShingle Brent M. Bijonowski
Jongkwon Park
Martin Bergert
Christina Teubert
Alba Diz-Muñoz
Milos Galic
Seraphine V. Wegner
Intercellular adhesion boots collective cell migration through elevated membrane tension
Nature Communications
title Intercellular adhesion boots collective cell migration through elevated membrane tension
title_full Intercellular adhesion boots collective cell migration through elevated membrane tension
title_fullStr Intercellular adhesion boots collective cell migration through elevated membrane tension
title_full_unstemmed Intercellular adhesion boots collective cell migration through elevated membrane tension
title_short Intercellular adhesion boots collective cell migration through elevated membrane tension
title_sort intercellular adhesion boots collective cell migration through elevated membrane tension
url https://doi.org/10.1038/s41467-025-56941-4
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