Nuclear lamin isoforms differentially contribute to LINC complex-dependent nucleocytoskeletal coupling and whole-cell mechanics
Name
vahabikashi-et-al-2022-nuclear-lamin-isoforms-differentially-contribute-to-linc-complex-dependent-nucleocytoskeletal.pdf
Description
Published version
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2.54 MB
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Checksum (MD5)
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Author(s)
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
Date Issued
April 26, 2022
Journal
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Citation
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).
Version
Final published version
Abstract
Significance
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.
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.
MIT Department
Massachusetts Institute of Technology. Department of Mechanical Engineering
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DOI of Published Version
https://doi.org/10.1073/pnas.2121816119
