ArticleProceedings of the National Academy of Sciences of the United States of America2019
Regulation of nuclear architecture, mechanics, and nucleocytoplasmic shuttling of epigenetic factors by cell geometric constraints.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 152 papers.
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Who cites it
152 citing papers in PubMed.
- Nuclear mechanotransduction: tools for mechanical perturbation and chromatin characterization.Nucleus (Austin, Tex.) · 2026Review
- Nuclear mechanobiology: a brief history and five unresolved questions.Nucleus (Austin, Tex.) · 2026Article
- Chromatin remodelling: a driving force in reverse mechanotransduction.RNA biology · 2026Review
- Nuclear Wrinkles Result From Geometric Adaptations to Cellular and Nuclear Morphological Changes in Epithelial Cells.Genes to cells : devoted to molecular & cellular mechanisms · 2026Article
- Mechanosensitive phosphorylation of NFATC4 at S213/S217 drives fibroblast-to-myofibroblast transition and fibrosis.The Journal of clinical investigation · 2026Article
- Beyond DNA damage: 3D tumor models and the integrin mechanobiology of radioresistance.Journal of experimental & clinical cancer research : CR · 2026Review
- Rhythms of growth: unveiling the mechanobiology behind heart maturation.The Journal of physiology · 2026Review
- Quantitative Analysis of Plasmid DNA Distribution and Transgene Expression Following Cell Squeezing.Annals of biomedical engineering · 2026Article
- Fibrillar adhesion dynamics govern the timescales of nuclear mechano-response via the vimentin cytoskeleton.Nature materials · 2026Article
- Quantifying intracellular mechanosensitive response upon spatially defined mechano-chemical triggering.eLife · 2026Article
- 3D-Printing-Assisted, Microfabricated Devices Reveal Hierarchical and Temporal Mechanosensing in High-Density Fibroblast Culture.ACS nano · 2026Article
- Vimentin molecular linkages with nesprin-3 enhance nuclear deformations by cell geometric constraints.Scientific reports · 2026Article
- Material-Induced Nuclear Deformation Controls Chromatin Architecture in Adipose Stem Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Architecture and regulation of nanoscale chromatin domains.Nature communications · 2026Review
- Deep Invaginations of Nuclear Envelope Coordinate Spatial Organization of Chromatin in Epithelium.bioRxiv : the preprint server for biology · 2026Article
- A Comprehensive Review of Nuclear Mechanics: Advances, Disease Relevance, Methodologies, and AI Applications.Cell biochemistry and biophysics · 2026Review
- 3D environment favors persistent changes in cell functions and altered morphology, wrinkling, and biomechanical signature of the nucleus.Cell reports. Physical science · 2026Article
- Stress vesicles link epidermal mechanotransduction to stem cell differentiation.Nature communications · 2026Article
- Phosphorylation-dependent modulation of the Lamin A/C-EZH2 complex regulates epithelial-mesenchymal plasticity.Nucleic acids research · 2026Article
- Extracellular matrix stiffness conditions glioblastoma cells for long-term migration: Mechanical memory as a driver of invasion and recurrence in glioblastoma.Neuro-oncology · 2026Review
92 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors.
Funding
Abstract
Cells sense mechanical signals from their microenvironment and transduce them to the nucleus to regulate gene expression programs. To elucidate the physical mechanisms involved in this regulation, we developed an active 3D chemomechanical model to describe the three-way feedback between the adhesions, the cytoskeleton, and the nucleus. The model shows local tensile stresses generated at the interface of the cell and the extracellular matrix regulate the properties of the nucleus, including nuclear morphology, levels of lamin A,C, and histone deacetylation, as these tensile stresses 1) are transmitted to the nucleus through cytoskeletal physical links and 2) trigger an actomyosin-dependent shuttling of epigenetic factors. We then show how cell geometric constraints affect the local tensile stresses and subsequently the three-way feedback and induce cytoskeleton-mediated alterations in the properties of the nucleus such as nuclear lamina softening, chromatin stiffening, nuclear lamina invaginations, increase in nuclear height, and shrinkage of nuclear volume. We predict a phase diagram that describes how the disruption of cytoskeletal components impacts the feedback and subsequently induce contractility-dependent alterations in the properties of the nucleus. Our simulations show that these changes in contractility levels can be also used as predictors of nucleocytoplasmic shuttling of transcription factors and the level of chromatin condensation. The predictions are experimentally validated by studying the properties of nuclei of fibroblasts on micropatterned substrates with different shapes and areas.
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