N-Cadherin based adhesion and Rac1 activity regulate tension polarization in the actin cortex
Abstract Tension-adhesion interplay is a crucial mechanism in multicellular organisms that determines the tension differential among internal and external interfaces, which in turn, mediates tissue surface tension and cell sorting, morphogenesis and remodeling, and cancer progression. Cadherins are...
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Nature Portfolio
2025-02-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-88537-9 |
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| author | Seyedsajad Moazzeni Kelly Kyker-Snowman Rick I. Cohen Huan Wang Ran Li David I. Shreiber Jeffrey D. Zahn Zheng Shi Hao Lin |
| author_facet | Seyedsajad Moazzeni Kelly Kyker-Snowman Rick I. Cohen Huan Wang Ran Li David I. Shreiber Jeffrey D. Zahn Zheng Shi Hao Lin |
| author_sort | Seyedsajad Moazzeni |
| collection | DOAJ |
| description | Abstract Tension-adhesion interplay is a crucial mechanism in multicellular organisms that determines the tension differential among internal and external interfaces, which in turn, mediates tissue surface tension and cell sorting, morphogenesis and remodeling, and cancer progression. Cadherins are widely believed to be involved, yet key aspects of the process are neither well characterized nor quantified. This study demonstrates the critical role of N-cadherin in driving tension polarization throughout the actin cortical network. N-cadherin regulates both tension increase at the cell-medium (external) interface and decrease at the cell-cell (internal) interface, and their quantitative magnitudes, both absolute and relative, strongly depend on the surface density of N-cadherin. Furthermore, the strength of tension polarization also increases with respect to the number of cell-cell interfaces for cells within a multicellular cluster. The cadherin-actin contractility linkage is mediated by Rac1, which serves as a molecular switch to trigger cortex remodeling and contraction via myosin II. Inhibition of Rac1 activity decreases tension polarization and leads to reduced coherence in both small clusters and spheroids. These results provide a pathway to reconcile opposing theories for tissue surface tension generation and perspectives in cancer treatment. |
| format | Article |
| id | doaj-art-a34f5c7b616a4e90b8fb1fd7f5d9f8bb |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-a34f5c7b616a4e90b8fb1fd7f5d9f8bb2025-02-09T12:37:13ZengNature PortfolioScientific Reports2045-23222025-02-0115111610.1038/s41598-025-88537-9N-Cadherin based adhesion and Rac1 activity regulate tension polarization in the actin cortexSeyedsajad Moazzeni0Kelly Kyker-Snowman1Rick I. Cohen2Huan Wang3Ran Li4David I. Shreiber5Jeffrey D. Zahn6Zheng Shi7Hao Lin8Department of Mechanical & Aerospace Engineering, Rutgers, The State University of New JerseyDepartment of Biomedical Engineering, Rutgers, The State University of New JerseyDepartment of Biomedical Engineering, Rutgers, The State University of New JerseyDepartment of Chemistry and Chemical Biology, Rutgers, The State University of New JerseyDepartment of Mechanical & Aerospace Engineering, Rutgers, The State University of New JerseyDepartment of Biomedical Engineering, Rutgers, The State University of New JerseyDepartment of Biomedical Engineering, Rutgers, The State University of New JerseyDepartment of Chemistry and Chemical Biology, Rutgers, The State University of New JerseyDepartment of Mechanical & Aerospace Engineering, Rutgers, The State University of New JerseyAbstract Tension-adhesion interplay is a crucial mechanism in multicellular organisms that determines the tension differential among internal and external interfaces, which in turn, mediates tissue surface tension and cell sorting, morphogenesis and remodeling, and cancer progression. Cadherins are widely believed to be involved, yet key aspects of the process are neither well characterized nor quantified. This study demonstrates the critical role of N-cadherin in driving tension polarization throughout the actin cortical network. N-cadherin regulates both tension increase at the cell-medium (external) interface and decrease at the cell-cell (internal) interface, and their quantitative magnitudes, both absolute and relative, strongly depend on the surface density of N-cadherin. Furthermore, the strength of tension polarization also increases with respect to the number of cell-cell interfaces for cells within a multicellular cluster. The cadherin-actin contractility linkage is mediated by Rac1, which serves as a molecular switch to trigger cortex remodeling and contraction via myosin II. Inhibition of Rac1 activity decreases tension polarization and leads to reduced coherence in both small clusters and spheroids. These results provide a pathway to reconcile opposing theories for tissue surface tension generation and perspectives in cancer treatment.https://doi.org/10.1038/s41598-025-88537-9Cadherin-based cell adhesionCortical tensionTension polarizationMechanotransductionMulticellular organizationMechanobiology |
| spellingShingle | Seyedsajad Moazzeni Kelly Kyker-Snowman Rick I. Cohen Huan Wang Ran Li David I. Shreiber Jeffrey D. Zahn Zheng Shi Hao Lin N-Cadherin based adhesion and Rac1 activity regulate tension polarization in the actin cortex Scientific Reports Cadherin-based cell adhesion Cortical tension Tension polarization Mechanotransduction Multicellular organization Mechanobiology |
| title | N-Cadherin based adhesion and Rac1 activity regulate tension polarization in the actin cortex |
| title_full | N-Cadherin based adhesion and Rac1 activity regulate tension polarization in the actin cortex |
| title_fullStr | N-Cadherin based adhesion and Rac1 activity regulate tension polarization in the actin cortex |
| title_full_unstemmed | N-Cadherin based adhesion and Rac1 activity regulate tension polarization in the actin cortex |
| title_short | N-Cadherin based adhesion and Rac1 activity regulate tension polarization in the actin cortex |
| title_sort | n cadherin based adhesion and rac1 activity regulate tension polarization in the actin cortex |
| topic | Cadherin-based cell adhesion Cortical tension Tension polarization Mechanotransduction Multicellular organization Mechanobiology |
| url | https://doi.org/10.1038/s41598-025-88537-9 |
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