Nuclear lamin isoforms differentially contribute to LINC complex-dependent nucleocytoskeletal coupling and whole-cell mechanics
<jats:title>Significance</jats:title> <jats:p>Interactions between the cell nucleus and cytoskeleton regulate cell mechanics and are facilitated by the interplay between the nuclear lamina and linker of nucleoskeleton and cytoskeleton (LINC) complexes. To date, the speci...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Proceedings of the National Academy of Sciences
2023
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| Online Access: | https://hdl.handle.net/1721.1/152524 |
| _version_ | 1826217042356731904 |
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| author | Vahabikashi, Amir Sivagurunathan, Suganya Nicdao, Fiona Ann Sadsad Han, Yu Long Park, Chan Young Kittisopikul, Mark Wong, Xianrong Tran, Joseph R Gundersen, Gregg G Reddy, Karen L Luxton, GW Gant Guo, Ming Fredberg, Jeffrey J Zheng, Yixian Adam, Stephen A Goldman, Robert D |
| author2 | Massachusetts Institute of Technology. Department of Mechanical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Mechanical Engineering Vahabikashi, Amir Sivagurunathan, Suganya Nicdao, Fiona Ann Sadsad Han, Yu Long Park, Chan Young Kittisopikul, Mark Wong, Xianrong Tran, Joseph R Gundersen, Gregg G Reddy, Karen L Luxton, GW Gant Guo, Ming Fredberg, Jeffrey J Zheng, Yixian Adam, Stephen A Goldman, Robert D |
| author_sort | Vahabikashi, Amir |
| collection | MIT |
| description | <jats:title>Significance</jats:title>
<jats:p>Interactions between the cell nucleus and cytoskeleton regulate cell mechanics and are facilitated by the interplay between the nuclear lamina and linker of nucleoskeleton and cytoskeleton (LINC) complexes. To date, the specific contribution of the four lamin isoforms to nucleocytoskeletal connectivity and whole-cell mechanics remains unknown. We discover that A- and B-type lamins distinctively interact with LINC complexes that bind F-actin and vimentin filaments to differentially modulate cortical stiffness, cytoplasmic stiffness, and contractility of mouse embryonic fibroblasts (MEFs). We propose and experimentally verify an integrated lamin–LINC complex–cytoskeleton model that explains cellular mechanical phenotypes in lamin-deficient MEFs. Our findings uncover potential mechanisms for cellular defects in human laminopathies and many cancers associated with mutations or modifications in lamin isoforms.</jats:p> |
| first_indexed | 2024-09-23T16:57:09Z |
| format | Article |
| id | mit-1721.1/152524 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T16:57:09Z |
| publishDate | 2023 |
| publisher | Proceedings of the National Academy of Sciences |
| record_format | dspace |
| spelling | mit-1721.1/1525242024-01-22T21:40:35Z Nuclear lamin isoforms differentially contribute to LINC complex-dependent nucleocytoskeletal coupling and whole-cell mechanics Vahabikashi, Amir Sivagurunathan, Suganya Nicdao, Fiona Ann Sadsad Han, Yu Long Park, Chan Young Kittisopikul, Mark Wong, Xianrong Tran, Joseph R Gundersen, Gregg G Reddy, Karen L Luxton, GW Gant Guo, Ming Fredberg, Jeffrey J Zheng, Yixian Adam, Stephen A Goldman, Robert D Massachusetts Institute of Technology. Department of Mechanical Engineering <jats:title>Significance</jats:title> <jats:p>Interactions between the cell nucleus and cytoskeleton regulate cell mechanics and are facilitated by the interplay between the nuclear lamina and linker of nucleoskeleton and cytoskeleton (LINC) complexes. To date, the specific contribution of the four lamin isoforms to nucleocytoskeletal connectivity and whole-cell mechanics remains unknown. We discover that A- and B-type lamins distinctively interact with LINC complexes that bind F-actin and vimentin filaments to differentially modulate cortical stiffness, cytoplasmic stiffness, and contractility of mouse embryonic fibroblasts (MEFs). We propose and experimentally verify an integrated lamin–LINC complex–cytoskeleton model that explains cellular mechanical phenotypes in lamin-deficient MEFs. Our findings uncover potential mechanisms for cellular defects in human laminopathies and many cancers associated with mutations or modifications in lamin isoforms.</jats:p> 2023-10-26T20:13:28Z 2023-10-26T20:13:28Z 2022-04-26 2023-10-26T20:07:38Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/152524 Vahabikashi, Amir, Sivagurunathan, Suganya, Nicdao, Fiona Ann Sadsad, Han, Yu Long, Park, Chan Young et al. 2022. "Nuclear lamin isoforms differentially contribute to LINC complex-dependent nucleocytoskeletal coupling and whole-cell mechanics." Proceedings of the National Academy of Sciences, 119 (17). en 10.1073/pnas.2121816119 Proceedings of the National Academy of Sciences Creative Commons Attribution Noncommercial No Derivatives http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Proceedings of the National Academy of Sciences Proceedings of the National Academy of Sciences |
| spellingShingle | Vahabikashi, Amir Sivagurunathan, Suganya Nicdao, Fiona Ann Sadsad Han, Yu Long Park, Chan Young Kittisopikul, Mark Wong, Xianrong Tran, Joseph R Gundersen, Gregg G Reddy, Karen L Luxton, GW Gant Guo, Ming Fredberg, Jeffrey J Zheng, Yixian Adam, Stephen A Goldman, Robert D Nuclear lamin isoforms differentially contribute to LINC complex-dependent nucleocytoskeletal coupling and whole-cell mechanics |
| title | Nuclear lamin isoforms differentially contribute to LINC complex-dependent nucleocytoskeletal coupling and whole-cell mechanics |
| title_full | Nuclear lamin isoforms differentially contribute to LINC complex-dependent nucleocytoskeletal coupling and whole-cell mechanics |
| title_fullStr | Nuclear lamin isoforms differentially contribute to LINC complex-dependent nucleocytoskeletal coupling and whole-cell mechanics |
| title_full_unstemmed | Nuclear lamin isoforms differentially contribute to LINC complex-dependent nucleocytoskeletal coupling and whole-cell mechanics |
| title_short | Nuclear lamin isoforms differentially contribute to LINC complex-dependent nucleocytoskeletal coupling and whole-cell mechanics |
| title_sort | nuclear lamin isoforms differentially contribute to linc complex dependent nucleocytoskeletal coupling and whole cell mechanics |
| url | https://hdl.handle.net/1721.1/152524 |
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