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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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InfluentialSelf-citationNa, J., Shi, Q., Yang, Z., Liu, Y., Chen, X., Wang, Z., Zheng, L., & Fan, Y. (2024) · The FASEB Journal · doi:10.1096/fj.202302178r · Cited by 19
“47 These functions are thought to be downstream of cytoplasmic signaling pathways and determined by gene expression.”
BackgroundHeterogeneous force response of chromatin in isolated nuclei
Bergamaschi, G., Biebricher, A. S., Witt, H., Byfield, F. J., Seymonson, X. M. R., Storm, C., Janmey, P. A., & Wuite, G. J. L. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114852 · Cited by 19
Rebalancing redox homeostasis: A pivotal regulator of the cGAS-STING pathway in autoimmune diseases
Zhao, Y., Xu, T., Wu, Z., Li, N., & Liang, Q. (2025) · Autoimmunity Reviews · doi:10.1016/j.autrev.2025.103823 · Cited by 21
Cytoskeletal safeguards: Protecting the nucleus from mechanical perturbations
Kechagia, Z., & Roca‐Cusachs, P. (2023) · Current Opinion in Biomedical Engineering · doi:10.1016/j.cobme.2023.100494 · Cited by 19
The dynamic nuclear envelope: resilience in health and dysfunction in disease
Turkmen, A. M., Saik, N. O., & Ullman, K. S. (2023) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2023.102230 · Cited by 19
Mistriotis, P., Wisniewski, E. O., Bishwa, R., Kaláb, P., & Κωνσταντόπουλος, Κ. (2024) · Trends in Cell Biology · doi:10.1016/j.tcb.2024.01.001 · Cited by 18
Pennacchio, F. A., Poli, A., Pramotton, F. M., Lavore, S., Rancati, I., Cinquanta, M., Vorselen, D., Prina, E., Romano, O. M., Ferrari, A., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-45168-4 · Cited by 19
“We also used a set of simple biophy-sicalmodels torationalize the results(seeSIAppendix) 19,20 .”
InfluentialPrinciples of organelle positioning in motile and non-motile cells
Kroll, J., & Renkawitz, J. (2024) · EMBO Reports · doi:10.1038/s44319-024-00135-4 · Cited by 21
“Due to the size and stiffness of the nucleus (Kalukula et al, 2022), cellular translocation through pores substantially smaller than the nucleus causes migration slowdown as the nucleus squeezes to fi t through the ECM pore (Calero-Cuenca et al, 2018; McGregor et al, 2016; Thiam et al, 2016; Harada…”
BackgroundExocrine gland–resident memory CD8 + T cells use mechanosensing for tissue surveillance
Ruef, N., Magdaleno, J. M., Ficht, X., Purvanov, V., Palayret, M., Wissmann, S., Pfenninger, P., Stolp, B., Thelen, F., de Albuquerque, J. B., et al. (2023) · Science Immunology · doi:10.1126/sciimmunol.add5724 · Cited by 16
Li, Y., Ji, Y., Meng, Y., Kim, Y., Lee, H., Kurian, A. G., Park, J., Yoon, J., Knowles, J. C., Choi, Y., et al. (2024) · Advanced Science · doi:10.1002/advs.202400586 · Cited by 18
Manning, G., Li, A., Eskndir, N., Currey, M. L., & Stephens, A. D. (2025) · Nucleus · doi:10.1080/19491034.2025.2486816 · Cited by 20
“Nuclear blebbing is important because it drives nuclear rupture [10,50].”
Self-citationThe nuclear periphery confers repression on H3K9me2-marked genes and transposons to shape cell fate
Marin, H. C., Allen, C., Simental, E., Martin, E. W., Panning, B., Al‐Sady, B., & Buchwalter, A. L. (2025) · Nature Cell Biology · doi:10.1038/s41556-025-01703-z · Cited by 20
“As the lamins and heterochromatin each absorb forces on the nucleus 65 , we tested whether forces induced by cellular spreading impair QKO viability by seeding cells on lower-attachment and higher-attachment substrates (Supplementary Fig.”
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Mechanoresponse of Curved Epithelial Monolayers Lining Bowl‐Shaped 3D Microwells
Luciano, M., Versaevel, M., Kalukula, Y., & Gabriele, S. (2023) · Advanced Healthcare Materials · doi:10.1002/adhm.202203377 · Cited by 18
Self-citationECM and epithelial stem cells: the scaffold of destiny
Estrach, S., Vivier, C.-M., & Féral, C. C. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1359585 · Cited by 21
Eskndir, N., Hossain, M., Currey, M. L., Pho, M., Berrada, Y., Lin, K. Y., Manning, G., Prince, K., & Stephens, A. D. (2024) · Molecular Biology of the Cell · doi:10.1091/mbc.e24-05-0232 · Cited by 20
“Loss of nuclear stiffness, shape, and integrity occurs in many human afflictions including aging, muscular dystrophy, heart disease, and many cancers (Stephens et al. , 2019a; Kalukula et al. , 2022).”
Self-citationPolarity-JaM: an image analysis toolbox for cell polarity, junction and morphology quantification
Giese, W., Albrecht, J. P., Oppenheim, O., Akmeriç, E. B., Kraxner, J., Schmidt, D., Harrington, K., & Gerhardt, H. (2025) · Nature Communications · doi:10.1038/s41467-025-56643-x · Cited by 18
“Changes in intracellular state or interactions with neighbouring cells can also induce changes in the shape of the cell and its organelles, in particular the nucleus (22).”
Mechanobiology of the cell nucleus
Lammerding, J., Engler, A. J., & Kamm, R. D. (2022) · APL Bioengineering · doi:10.1063/5.0135299 · Cited by 17
Self-citationLamins as structural nuclear elements through evolution
Odell, J., & Lammerding, J. (2023) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2023.102267 · Cited by 17
Self-citationMa, T., Liu, X., Su, H., Shi, Q., He, Y., Wu, F., Gao, C., Li, K., Liang, Z., Zhang, D., et al. (2023) · Advanced Science · doi:10.1002/advs.202305867 · Cited by 17
Insights into the mechanobiology of cancer metastasis via microfluidic technologies
Liang, L., Song, X., Zhao, H., & Lim, C. T. (2024) · APL Bioengineering · doi:10.1063/5.0195389 · Cited by 19
Confined Migration Drives Stem Cell Differentiation
Gao, X., Li, Y., Lee, J. W. N., Zhou, J., Rangaraj, V., Marlena, J., & Holle, A. W. (2025) · Advanced Science · doi:10.1002/advs.202415407 · Cited by 17
Viscoelastic mechanics of living cells
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Chu, C. G., Lang, N., Walsh, E., Zheng, M., Manning, G., Shalin, K., Cunha, L. M., Faucon, K. E., Kam, N., Folan, S. N., et al. (2025) · Journal of Cell Science · doi:10.1242/jcs.263945 · Cited by 20
“Nuclear rupture has been reported to cause dysfunction via increased DNA damage, transcriptional changes and loss of cell cycle control (Kalukula et al., 2022).”
InfluentialSelf-citationGignac, S. J., MacCharles, K. R., Fu, K., Bonaparte, K., Akarsu, G., Barrett, T. W., Verheyen, E. M., & Richman, J. M. (2023) · Disease Models & Mechanisms · doi:10.1242/dmm.049844 · Cited by 12
“Thus, the appearance of irregularly shaped chondrocyte lacunae is connected to abnormal nuclear shape and could reflect abnormal stresses in the cytoskeleton caused by the variants (Kalukula et al., 2022; Long and Lammerding, 2021).”
Biomimetic Alveoli System with Vivid Mechanical Response and Cell–Cell Interface
Niu, M., Zhu, Y., Ding, X., Zu, Y., Zhao, Y., & Wang, Y. (2023) · Advanced Healthcare Materials · doi:10.1002/adhm.202300850 · Cited by 16
Fluid and Bubble Flow Detach Adherent Cancer Cells to Form Spheroids on a Random Positioning Machine
Cortés-Sánchez, J. L., Melnik, D., Sandt, V., Kahlert, S., Marchal, S., Johnson, I. R. D., Calvaruso, M., Liemersdorf, C., Wüest, S. L., Grimm, D. G., et al. (2023) · Cells · doi:10.3390/cells12222665 · Cited by 16
“This pressure compresses the cells and the nuclei, which can also promote the nuclear transport of transcription factors (Figure 2B) [24].”
BackgroundProcès, A., Alpizar, Y. A., Halliez, S., Brône, B., Saudou, F., Ris, L., & Gabriele, S. (2023) · Biomaterials · doi:10.1016/j.biomaterials.2023.122426 · Cited by 17
Self-citationN-terminal tags impair the ability of lamin A to provide structural support to the nucleus
Odell, J., & Lammerding, J. (2024) · Journal of Cell Science · doi:10.1242/jcs.262207 · Cited by 18
Self-citationSaram, P. D., Nguyen, N., Jamali, S. S., & Kashaninejad, N. (2024) · Small Science · doi:10.1002/smsc.202400410 · Cited by 16
Shin, S. J., Bayarkhangai, B., Tsogtbaatar, K., Yuxuan, M., Kim, S., Kim, Y., Taghizadeh, A., Kim, D., Kim, D., Lee, J., et al. (2025) · Advanced Science · doi:10.1002/advs.202403409 · Cited by 17
“The interaction of TFs with the actin cytoskeleton or the direct coupling of the cytoskeleton to nuclear pore complexes (NPCs) that open in response to mechanical forces play a role in the nuclear translocation of TFs and transcriptional coactivators 49-53 .”
BackgroundThe emerging roles of the endoplasmic reticulum in mechanosensing and mechanotransduction
Townson, J., & Progida, C. (2025) · Journal of Cell Science · doi:10.1242/jcs.263503 · Cited by 15
Emerging mechanobiology techniques to probe intracellular mechanics
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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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