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Mechanics and functional consequences of nuclear deformations
Open accessAbstract
As the home of cellular genetic information, the nucleus has a critical role in determining cell fate and function in response to various signals and stimuli. In addition to biochemical inputs, the nucleus is constantly exposed to intrinsic and extrinsic mechanical forces that trigger dynamic changes in nuclear structure and morphology. Emerging data suggest that the physical deformation of the nucleus modulates many cellular and nuclear functions. These functions have long been considered to be downstream of cytoplasmic signalling pathways and dictated by gene expression. In this Review, we discuss an emerging perspective on the mechanoregulation of the nucleus that considers the physical connections from chromatin to nuclear lamina and cytoskeletal filaments as a single mechanical unit. We describe key mechanisms of nuclear deformations in time and space and provide a critical review of the structural and functional adaptive responses of the nucleus to deformations. We then consider the contribution of nuclear deformations to the regulation of important cellular functions, including muscle contraction, cell migration and human disease pathogenesis. Collectively, these emerging insights shed new light on the dynamics of nuclear deformations and their roles in cellular mechanobiology.
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“Concurrently, mechanical stress induces nuclear deformation, directly increasing chromatin accessibility at mechanosensitive enhancers near genes such as ACTA2 and COL1A1 (123-125).”
From The mechanotransduction-immune axis in organ fibrosis: dual regulatory mechanisms and translational therapeutic perspectives (2025) · cites this paper as [123]
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“These extracellular stimuli are transduced through intracellular mediators, including the YAP/TAZ pathway, and transmitted to the nucleus via cytoskeletal networks that physically couple membrane-bound receptors to nuclear architecture and chromatin organization [15,16].”
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Metadata
- Authors
- Kalukula, Y., Stephens, A. D., Lammerding, J., & Gabriele, S.
- Affiliations
- University of Mons (BE)
- University of Massachusetts Amherst (US)
- Cornell University (US)
- Corresponding author
- Lammerding, Jan
- Gabriele, Sylvain
- Venue
- Nature Reviews Molecular Cell Biology
- Published
- 2022-05-05
- Volume
- 23
- Issue
- 9
- Pages
- 583-602
- ISSN
- 1471-0072 (ISSN-L)
- 1471-0080
- PMC
- PMC9902167
- OpenAlex
- W4229069131
- Cited by
- 475
- References
- 291
- Citations by year
- 2026: 111 · 2025: 154 · 2024: 116 · 2023: 77 · 2022: 15
- FWCI
- 9.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Reviews Molecular Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- ORBi UMONS (submittedVersion, other-oa)
- Funders
- National Science Foundation (2022048, U54CA210184)
- Volkswagen Foundation (96733)
- Fonds De La Recherche Scientifique - FNRS (T.0092.21)
- Vlaamse regering
- National Institutes of Health
- Fonds pour la Formation à la Recherche dans l’Industrie et dans l’Agriculture
- European Regional Development Fund (1510614)
- National Heart, Lung, and Blood Institute (R01HL082792)
- National Human Genome Research Institute (UM1HG011536)
- National Cancer Institute (U54CA210184)
- National Institute of General Medical Sciences (R01GM137605, R00GM123195)
- Interreg
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Keywords
- nuclear deformation, mechanobiology, nuclear mechanics, nuclear lamina, chromatin, cytoskeletal filaments, genome organization, cell migration, muscle contraction, signal transduction
- MeSH terms
- Cell Differentiation, Cell Nucleus, Chromatin, Cytoskeleton, Humans, Signal Transduction
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