Nucleo-cytoskeletal coupling controls intracellular deformation partitioning during cell stretching
Cells sense and transduce mechanical forces to regulate diverse biological processes, yet the mechanical stimuli that initiate these processes remain poorly understood. In particular, how nuclear and cytoplasmic deformations respond to external forces is unclear. Here, we developed a microscopy-base...
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| Format: | Article |
| Language: | English |
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The Royal Society
2025-07-01
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| Series: | Royal Society Open Science |
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| Online Access: | https://royalsocietypublishing.org/doi/10.1098/rsos.250409 |
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| author | Jerry Chen Iris Sloan Alexandra Bermudez David Choi Ming-Heng Tsai Lihua Jin Jimmy K Hu Neil Lin |
| author_facet | Jerry Chen Iris Sloan Alexandra Bermudez David Choi Ming-Heng Tsai Lihua Jin Jimmy K Hu Neil Lin |
| author_sort | Jerry Chen |
| collection | DOAJ |
| description | Cells sense and transduce mechanical forces to regulate diverse biological processes, yet the mechanical stimuli that initiate these processes remain poorly understood. In particular, how nuclear and cytoplasmic deformations respond to external forces is unclear. Here, we developed a microscopy-based technique to quantify the extensional uniaxial strains of the nucleus and cytoplasm during cell stretching, enabling direct measurement of their bulk mechanical responses. Using this approach, we identified a previously unrecognized inverse relationship between nuclear and cytoplasmic deformation in epithelial monolayers. We demonstrate that nucleo-cytoskeletal coupling, mediated by the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex, regulates this anti-correlation (Pearson correlation coefficient approx. 0.3). Disrupting LINC abolished this relationship, revealing its fundamental role in intracellular deformation partitioning. Furthermore, we found that cytoplasmic deformation is directly correlated with stretch-induced nuclear shrinkage, suggesting a mechanotransduction pathway in which cytoplasmic mechanics influence nuclear responses. Lastly, multivariable analyses established that intracellular deformation can be inferred from cell morphology, providing a predictive framework for cellular mechanical behaviour. These findings refine our understanding of nucleo-cytoskeletal coupling in governing intracellular force transmission and mechanotransduction. |
| format | Article |
| id | doaj-art-cbcbd2ddee744fb49bbfec13bb890cdd |
| institution | Kabale University |
| issn | 2054-5703 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | The Royal Society |
| record_format | Article |
| series | Royal Society Open Science |
| spelling | doaj-art-cbcbd2ddee744fb49bbfec13bb890cdd2025-08-20T03:56:05ZengThe Royal SocietyRoyal Society Open Science2054-57032025-07-0112710.1098/rsos.250409Nucleo-cytoskeletal coupling controls intracellular deformation partitioning during cell stretchingJerry Chen0Iris Sloan1Alexandra Bermudez2David Choi3Ming-Heng Tsai4Lihua Jin5Jimmy K Hu6Neil Lin7University of California Los Angeles, Los Angeles, CA, USAUniversity of California Los Angeles, Los Angeles, CA, USAUniversity of California Los Angeles, Los Angeles, CA, USAUniversity of California Los Angeles, Los Angeles, CA, USAUniversity of California Los Angeles, Los Angeles, CA, USAUniversity of California Los Angeles, Los Angeles, CA, USAUniversity of California Los Angeles, Los Angeles, CA, USAUniversity of California Los Angeles, Los Angeles, CA, USACells sense and transduce mechanical forces to regulate diverse biological processes, yet the mechanical stimuli that initiate these processes remain poorly understood. In particular, how nuclear and cytoplasmic deformations respond to external forces is unclear. Here, we developed a microscopy-based technique to quantify the extensional uniaxial strains of the nucleus and cytoplasm during cell stretching, enabling direct measurement of their bulk mechanical responses. Using this approach, we identified a previously unrecognized inverse relationship between nuclear and cytoplasmic deformation in epithelial monolayers. We demonstrate that nucleo-cytoskeletal coupling, mediated by the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex, regulates this anti-correlation (Pearson correlation coefficient approx. 0.3). Disrupting LINC abolished this relationship, revealing its fundamental role in intracellular deformation partitioning. Furthermore, we found that cytoplasmic deformation is directly correlated with stretch-induced nuclear shrinkage, suggesting a mechanotransduction pathway in which cytoplasmic mechanics influence nuclear responses. Lastly, multivariable analyses established that intracellular deformation can be inferred from cell morphology, providing a predictive framework for cellular mechanical behaviour. These findings refine our understanding of nucleo-cytoskeletal coupling in governing intracellular force transmission and mechanotransduction.https://royalsocietypublishing.org/doi/10.1098/rsos.250409nucleo-cytoskeletal couplingcell stretchingimage-based measurementstrain measurementcell mechanicssystems biology |
| spellingShingle | Jerry Chen Iris Sloan Alexandra Bermudez David Choi Ming-Heng Tsai Lihua Jin Jimmy K Hu Neil Lin Nucleo-cytoskeletal coupling controls intracellular deformation partitioning during cell stretching Royal Society Open Science nucleo-cytoskeletal coupling cell stretching image-based measurement strain measurement cell mechanics systems biology |
| title | Nucleo-cytoskeletal coupling controls intracellular deformation partitioning during cell stretching |
| title_full | Nucleo-cytoskeletal coupling controls intracellular deformation partitioning during cell stretching |
| title_fullStr | Nucleo-cytoskeletal coupling controls intracellular deformation partitioning during cell stretching |
| title_full_unstemmed | Nucleo-cytoskeletal coupling controls intracellular deformation partitioning during cell stretching |
| title_short | Nucleo-cytoskeletal coupling controls intracellular deformation partitioning during cell stretching |
| title_sort | nucleo cytoskeletal coupling controls intracellular deformation partitioning during cell stretching |
| topic | nucleo-cytoskeletal coupling cell stretching image-based measurement strain measurement cell mechanics systems biology |
| url | https://royalsocietypublishing.org/doi/10.1098/rsos.250409 |
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