Matrix stiffness drives drop like nuclear deformation and lamin A/C tension-dependent YAP nuclear localization
Abstract Extracellular matrix (ECM) stiffness influences cancer cell fate by altering gene expression. Previous studies suggest that stiffness-induced nuclear deformation may regulate gene expression through YAP nuclear localization. We investigated the role of the nuclear lamina in this process. We...
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Nature Portfolio
2024-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54577-4 |
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| author | Ting-Ching Wang Samere Abolghasemzade Brendan P. McKee Ishita Singh Kavya Pendyala Mohammad Mohajeri Hailee Patel Aakansha Shaji Anna L. Kersey Kajol Harsh Simran Kaur Christina R. Dollahon Sasanka Chukkapalli Pushkar P. Lele Daniel E. Conway Akhilesh K. Gaharwar Richard B. Dickinson Tanmay P. Lele |
| author_facet | Ting-Ching Wang Samere Abolghasemzade Brendan P. McKee Ishita Singh Kavya Pendyala Mohammad Mohajeri Hailee Patel Aakansha Shaji Anna L. Kersey Kajol Harsh Simran Kaur Christina R. Dollahon Sasanka Chukkapalli Pushkar P. Lele Daniel E. Conway Akhilesh K. Gaharwar Richard B. Dickinson Tanmay P. Lele |
| author_sort | Ting-Ching Wang |
| collection | DOAJ |
| description | Abstract Extracellular matrix (ECM) stiffness influences cancer cell fate by altering gene expression. Previous studies suggest that stiffness-induced nuclear deformation may regulate gene expression through YAP nuclear localization. We investigated the role of the nuclear lamina in this process. We show that the nuclear lamina exhibits mechanical threshold behavior: once unwrinkled, the nuclear lamina is inextensible. A computational model predicts that the unwrinkled lamina is under tension, which is confirmed using a lamin tension sensor. Laminar unwrinkling is caused by nuclear flattening during cell spreading on stiff ECM. Knockdown of lamin A/C eliminates nuclear surface tension and decreases nuclear YAP localization. These findings show that nuclear deformation in cells conforms to the nuclear drop model and reveal a role for lamin A/C tension in controlling YAP localization in cancer cells. |
| format | Article |
| id | doaj-art-507897aa058a4717b51d68fe1a3bd140 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-507897aa058a4717b51d68fe1a3bd1402024-11-24T12:34:07ZengNature PortfolioNature Communications2041-17232024-11-0115111710.1038/s41467-024-54577-4Matrix stiffness drives drop like nuclear deformation and lamin A/C tension-dependent YAP nuclear localizationTing-Ching Wang0Samere Abolghasemzade1Brendan P. McKee2Ishita Singh3Kavya Pendyala4Mohammad Mohajeri5Hailee Patel6Aakansha Shaji7Anna L. Kersey8Kajol Harsh9Simran Kaur10Christina R. Dollahon11Sasanka Chukkapalli12Pushkar P. Lele13Daniel E. Conway14Akhilesh K. Gaharwar15Richard B. Dickinson16Tanmay P. Lele17Artie McFerrin Department of Chemical Engineering, Texas A&M UniversityDepartment of Biomedical Engineering, Texas A&M UniversityDepartment of Biomedical Engineering, Texas A&M UniversityDepartment of Biomedical Engineering, Texas A&M UniversityDepartment of Biomedical Engineering, Texas A&M UniversityDepartment of Biomedical Engineering, Texas A&M UniversityDepartment of Biomedical Engineering, Texas A&M UniversityArtie McFerrin Department of Chemical Engineering, Texas A&M UniversityDepartment of Biomedical Engineering, Texas A&M UniversityDepartment of Biomedical Engineering, Texas A&M UniversityDepartment of Biomedical Engineering, Texas A&M UniversityDepartment of Biomedical Engineering, Texas A&M UniversityDepartment of Biomedical Engineering, Texas A&M UniversityArtie McFerrin Department of Chemical Engineering, Texas A&M UniversityDepartment of Biomedical Engineering, The Ohio State UniversityDepartment of Biomedical Engineering, Texas A&M UniversityDepartment of Chemical Engineering, University of FloridaArtie McFerrin Department of Chemical Engineering, Texas A&M UniversityAbstract Extracellular matrix (ECM) stiffness influences cancer cell fate by altering gene expression. Previous studies suggest that stiffness-induced nuclear deformation may regulate gene expression through YAP nuclear localization. We investigated the role of the nuclear lamina in this process. We show that the nuclear lamina exhibits mechanical threshold behavior: once unwrinkled, the nuclear lamina is inextensible. A computational model predicts that the unwrinkled lamina is under tension, which is confirmed using a lamin tension sensor. Laminar unwrinkling is caused by nuclear flattening during cell spreading on stiff ECM. Knockdown of lamin A/C eliminates nuclear surface tension and decreases nuclear YAP localization. These findings show that nuclear deformation in cells conforms to the nuclear drop model and reveal a role for lamin A/C tension in controlling YAP localization in cancer cells.https://doi.org/10.1038/s41467-024-54577-4 |
| spellingShingle | Ting-Ching Wang Samere Abolghasemzade Brendan P. McKee Ishita Singh Kavya Pendyala Mohammad Mohajeri Hailee Patel Aakansha Shaji Anna L. Kersey Kajol Harsh Simran Kaur Christina R. Dollahon Sasanka Chukkapalli Pushkar P. Lele Daniel E. Conway Akhilesh K. Gaharwar Richard B. Dickinson Tanmay P. Lele Matrix stiffness drives drop like nuclear deformation and lamin A/C tension-dependent YAP nuclear localization Nature Communications |
| title | Matrix stiffness drives drop like nuclear deformation and lamin A/C tension-dependent YAP nuclear localization |
| title_full | Matrix stiffness drives drop like nuclear deformation and lamin A/C tension-dependent YAP nuclear localization |
| title_fullStr | Matrix stiffness drives drop like nuclear deformation and lamin A/C tension-dependent YAP nuclear localization |
| title_full_unstemmed | Matrix stiffness drives drop like nuclear deformation and lamin A/C tension-dependent YAP nuclear localization |
| title_short | Matrix stiffness drives drop like nuclear deformation and lamin A/C tension-dependent YAP nuclear localization |
| title_sort | matrix stiffness drives drop like nuclear deformation and lamin a c tension dependent yap nuclear localization |
| url | https://doi.org/10.1038/s41467-024-54577-4 |
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