Image-based Strain Analysis Reveals Intracellular Strain Controlled by Nucleo-Cytoskeletal Coupling
Image-based Strain Analysis Reveals Intracellular Strain Controlled by Nucleo-Cytoskeletal Coupling
ABSTRACT Cells can sense and transduce mechanical forces, such as stretching, and convert these signals into diverse cell biological events. While much effort has been devoted to identifying the downstream biochemical and cellular responses, it is equally crucial to pinpoint the mechanical stimuli within a cell driving these responses. Specifically, much remains unknown about how intracellular strains are distributed and controlled during mechanical deformation. In this study, we developed a microscopy-based intracellular strain measurement technique. Utilizing the intrapopulation mechanical heterogeneity of epithelial monolayers, we observed an inverse relationship between cytoplasmic and nuclear strains. We found that this anti-correlation is abolished by the inhibition of Linker of Nucleoskeleton and Cytoskeleton (LINC) complex, suggesting that nucleo-cytoskeletal coupling controls intracellular strain distribution. We discovered a direct connection between cytoplasmic strain and stretch-induced nucleus size changes, implying that molecular events arising from cytoplasmic deformation may drive nuclear remodeling during stretching. By conducting multivariable analyses, we found that the intracellular strain can be inferred from cell morphology. Overall, our experimental platform and findings provide a foundation for unraveling the relationship between mechanotransduction pathways and upstream intracellular strain. SIGNIFICANCEMechanical stimuli exert influence on epithelial cells, not only orchestrating embryogenesis and regeneration, but also regulating cancer progression and inflammatory conditions. Despite efforts to identify mechanically activated molecular events, understanding how deformation is distributed within cells to induce subcellular responses remains limited. Specifically, the control of subcellular strain distribution during mechanical stretch is unclear. In this study, we developed a microscopy-based method to measure subcellular strain and observed an inverse relationship between cytoplasmic and nuclear strains. Disrupting nucleo-cytoplasmic coupling abolished this relationship, suggesting its role in controlling strain distribution. Additionally, we found that cytoplasmic strain correlates with nucleus size changes during stretching, indicating cytoplasmic events influence nucleus remodeling.
Lin Neil Y.C.、Bermudez Alexandra、Jin Lihua、Sloan Iris、Choi David、Tsai Ming-Heng、Hu Jimmy K.、Chen Jerry C.C.
Bioengineering Department, University of California||Mechanical and Aerospace Engineering Department, University of California||Broad Stem Cell Center, University of California||Jonsson Comprehensive Cancer Center, University of California||Institute for Quantitative and Computational Biosciences, University of CaliforniaBioengineering Department, University of CaliforniaMechanical and Aerospace Engineering Department, University of CaliforniaBioengineering Department, University of CaliforniaMechanical and Aerospace Engineering Department, University of CaliforniaSchool of Dentistry, University of California||Molecular Biology Institute, University of California||Broad Stem Cell Center, University of CaliforniaSchool of Dentistry, University of California||Molecular Biology Institute, University of California||Broad Stem Cell Center, University of CaliforniaBioengineering Department, University of California
细胞生物学生物物理学生物科学研究方法、生物科学研究技术
Lin Neil Y.C.,Bermudez Alexandra,Jin Lihua,Sloan Iris,Choi David,Tsai Ming-Heng,Hu Jimmy K.,Chen Jerry C.C..Image-based Strain Analysis Reveals Intracellular Strain Controlled by Nucleo-Cytoskeletal Coupling[EB/OL].(2025-03-28)[2025-06-06].https://www.biorxiv.org/content/10.1101/2024.04.18.590162.点此复制
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