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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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Mechanobiology of Collective Cell Migration in 3D Microenvironments
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Editorial: Nuclear morphology in development and disease
Lele, T. P., Levy, D. L., & Mishra, K. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1267645 · Cited by 3
“While some mechanisms responsible for determining nuclear morphology have been elucidated (Lele et al., 2018; Kalukula et al., 2022), much less is known about how nuclear morphology becomes altered in disease and whether nuclear morphology directly impacts cell function.”
BackgroundYAP localization mediates mechanical adaptation of human cancer cells during extravasation in vivoPreprint
So, W. Y., Wong, C. S., Azubuike, U. F., Paul, C. D., Sangsari, P. R., Gordon, P. B., Gong, H., Maity, T. K., Lim, P., Yang, Z., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.11.14.567015 · Cited by 4
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“66, 67 In this view, the nucleus acts as a dynamic biomechanical sensor of intrinsic and extrinsic mechanical forces according to which it can adapt changes to its shape and function.”
BackgroundD’Annunzio, S., Santomaso, L., Michelatti, D., Bernardis, C., Vitali, G., Lago, S., Testi, C., Pontecorvo, E., Poli, A., Pennacchio, F. A., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.05.06.592652 · Cited by 3
Coaching ribosome biogenesis from the nuclear peripheryPreprint
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“MMP2 expression could be controlled by stress-induced signaling via nuclear compression of PPE cells 56,57 , mechano-sensitive channels 58 and/or via the Hippo/YAP pathway 59 .”
Tomida, K., Kim, J., MAEDA, E., ADACHI, T., & MATSUMOTΟ, T. (2024) · Cell and Tissue Research · doi:10.1007/s00441-024-03905-7 · Cited by 2
“Numerous literatures reported the biological significance of cellular and nuclear morphology as they indicate the mechanical state that influences downstream functionality such as chromatin conformation and, in turn, transcriptional activities (Amar et al. 2021; Kalukula et al. 2022).”
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Regulation of p65 nuclear localization and chromatin states by compressive force
Gupta, R., Schärer, P., Liao, Y., Roy, B., Benoit, R., & Shivashankar, G. V. (2025) · Molecular Biology of the Cell · doi:10.1091/mbc.e23-11-0431 · Cited by 2
“However, the cellular and nuclear response to the microenvironmental signals has not been fully explored (Kalukula et al. , 2022).”
Bermudez, A. G., Latham, Z. D., Ma, A. J., Bi, D., Hu, J. K., & Lin, N. Y. C. (2025) · Communications Biology · doi:10.1038/s42003-025-07677-w · Cited by 3
“Speci fi cally, we characterized both the cellular and nuclear sizes, as the nucleus contains key architectural structures that interact with the genome 28,29 and has been shown to be an important organelle in mechanotransduction 30,31 .”
The dilemma of nuclear mechanical forces in DNA damage and repair
Ali, I., Xu, F., Qin, P., & Qiu, J. (2025) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2025.151639 · Cited by 3
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“At the subcellular and molecular levels, forces are transmitted from extra-cellular matrix to nucleus through various mechanisms, including protein conformational changes [36], integrin-adhesion [37], cell–cell adhesion [38], cytoskeleton [39], nuclear mechanotransduction [40] and ion channels [41].”
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Direct mechanical communication of cellular to nuclear shapes in oocytes
Vos, B. E., Vadapalli, Y., Muenker, T. M., Jentoft, I. M. A., Todisco, E., Eskandari, M. A., Schuh, M., Lénárt, P., & Betz, T. (2025) · Biophysical Journal · doi:10.1016/j.bpj.2025.08.012 · Cited by 2
“However, as the nucleus is a multicomponent organelle with distinct properties (3,4,27), a full mechanical characterization requires knowledge of the intranuclear properties over a wide range of biologically relevant timescales.”
Molecular basis of the activity of a photoswitchable histone deacetylase inhibitor
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CTCF maintains centromere function and mitotic fidelity
Walsh, E., Laskarzewski, T., Maresca, T. J., & Stephens, A. D. (2026) · Journal of Cell Science · doi:10.1242/jcs.264181 · Cited by 2
“…post-mitotic nuclear reformation We reasoned that mitotic failures or even slight disruptions in mitosis could manifest during the post-mitosis nuclear reformation as an abnormal nuclear shape, a hallmark of human disease that can cause dysfunction (Stephens et al., 2019; Kalukula et al., 2022).”
Self-citationDynamins maintain nuclear envelope homeostasis and genome stability
Aveleira, C. A., Martial, T., Carrique, L., Gaspar, R., Caulino‐Rocha, A., Myatt, I., Wendler, F., Lascaux, P., Claire, M. L., Bancroft, J. M., et al. (2026) · Nature Communications · doi:10.1038/s41467-025-68130-4 · Cited by 3
“Thus, we explored the role of membrane-binding dynamins in the homeostasis of the NE. Employing engineered mouse fi broblasts in which dynamins 1, 2, and 3 expression is blocked upon 4-hydroxytamoxifen (4-OHT) treatment 20 (henceforth dynamin-TKO; produced asdetailed in SupplementaryFig.”
Zeng, H.-T., Yang, Y., Tan, H., Wang, Z., Hao, T.-T., Zhang, Q.-Q., & Guo, Z.-Y. (2026) · Microchemical journal (Print) · doi:10.1016/j.microc.2026.117275 · Cited by 2
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“These nuclear deformations are not merely structural but actively regulate chromatin organization and mechanosensitive gene expression associated with lineage specification [76,77].”
Nuclear Mechanics and Nuclear Mechanotransduction in Cancer Cell Migration and Invasion
Mierke, C. T. (2026) · Biomolecules · doi:10.3390/biom16030457 · Cited by 2
Srivastava, L. K., Ghagre, A., Duchastel-Vassaramva, I., & Ehrlicher, A. J. (2026) · Journal of Cell Science · doi:10.1242/jcs.264519 · Cited by 2
“…architecture and the trafficking of mechanosensitive transcription factors, such as YAP (also known as YAP1) (Damodaran et al., 2018; Seelbinder et al., 2021; Kalukula et al., 2022; Elosegui-Artola et al., 2017), alterations in nuclear stiffness might profoundly affect cell fate and function.”
Peng, H., Qiao, R., Qiao, J., Gao, Y., & Dong, B. (2026) · Journal of Cell Science · doi:10.1242/jcs.264699 · Cited by 2
Ai, Y., & Zhou, J. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1849535 · Cited by 2
“…burgeoning field investigating how forces transmitted to the nucleus reshape chromatin architecture and epigenetic landscapes—has opened entirely new avenues for understanding how physical forces may regulate the epigenetic programs that maintain GSC identity (Kalukula et al., 2022).”
Mechanobiologically dynamic biomaterials for tissue healing and disease treatment
Lee, J., Yun, Y. G., Shenoy, V. B., Leong, K. W., & Kim, H. (2026) · Cell Biomaterials · doi:10.1016/j.celbio.2026.100536 · Cited by 4
Substrate heterogeneity promotes cancer cell dissemination through interface roughening
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Monte-Monge, A. D., de Lara, Í. R.-P., Gonzalo, P., Espinós‐Estévez, C., González‐Amor, M., de la Fuente‐Pérez, M., Andrés‐Manzano, M. J., Fanjul, V., Gimeno, J. R., Villa, R. B., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241311172 · Cited by 2
“Alterations in gene expression and function in lamin A/C-deficient VSMCs and ECs are likely caused by defective mechanotransduction and altered signaling, transcription, and chromatin organization, which are key processes that are regulated by A-type lamins [4,6].”
Background[Hot Topics and Emerging Trends in Mechanobiology Research].
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A reciprocal theorem for biphasic poro-viscoelastic materials
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Constructing polymorphonuclear cells: chromatin folding shapes nuclear morphology
Murre, C., Patta, I., Mishra, S. V., & Hu, M. (2024) · Trends in Immunology · doi:10.1016/j.it.2024.09.012 · Cited by 2
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“The expression tendency of H3K4me3 was opposite of H3K9me3, consistent with the notion that H3K9me3 and H3K27me3 are involved in chromatin condensation but H3K4me4 is associated with chromatin decondensation [58].”
Adhesion-controlled mechanics of the glial niche regulate neural stem cell proliferative potential
Cristina, A. S., Letort, G., Perthame, É., Rigaud, S. U., Briand, D., Kukde, A., Banach-Latapy, A., Owens, N. D. L., Valon, L., Tinévez, J.-Y., et al. (2026) · Developmental Cell · doi:10.1016/j.devcel.2026.04.011 · Cited by 2
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“Also, identification of deviations from normal nuclear morphologies are important indicators of diseases such as cancer or premature aging syndrome [9].”
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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