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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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Ayushman, M., Lee, H. P., Agarwal, P., Mikos, G., Tong, X., Jones, S., Sinha, S., Goodman, S. B., Bhutani, N., & Yang, F. (2024) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.37861 · Cited by 7
Protecting centrosomes from fracturing enables efficient cell navigation
Schmitt, M. T., Kroll, J., Ruiz-Fernandez, M. J. A., Hauschild, R., Ghosh, S., Kameritsch, P., Merrin, J., Schmid, J., Stefanowski, K., Thomae, A. W., et al. (2025) · Science Advances · doi:10.1126/sciadv.adx4047 · Cited by 7
“Further, these findings add to the emerging concept that intracellular organelles are not only actively positioned ( 18 , 52 – 54 ) but also experience physical forces ( 55 , 56 ), requiring their shielding to maintain cellular functionality.”
Mechanical regulation and activity of nuclear condensates
Zhao, J. Z., Xia, J., & Brangwynne, C. P. (2025) · Biophysical Journal · doi:10.1016/j.bpj.2025.10.009 · Cited by 7
Wu, G., Chen, S., Li, Q., Zhang, M., Cao, F., Wei, J., Guo, L., Li, P., Wei, X., & Zhang, Q. (2025) · Mechanobiology in Medicine · doi:10.1016/j.mbm.2025.100164 · Cited by 9
“92 Under mechanical stress, it undergoes conformational changes that expose binding sites, recruiting chromatin remodeling complexes to perinuclear heterochromatin regions to repress or activate specific genes.”
Mechanotransduction by nuclear envelope tension
Rajan, S. G., Roca‐Cusachs, P., & Niethammer, P. (2025) · Nucleus · doi:10.1080/19491034.2025.2600901 · Cited by 8
“The NE is a composite structure of two lipid bilayers – the outer and inner nuclear membranes (ONM/INM) – fused at nuclear pores and mechanically stabilized by an intermediate-filament lamina composed of lamins A/C and B1/B2 (Figure 2) [3].”
The Mechanobiologist’s dilemma: Force, stiffness, and the illusion of adaptation
Issler, M., Colin‐York, H., & Fritzsche, M. (2026) · Mechanobiology · doi:10.1177/29780241251412505 · Cited by 7
Nuclear mechanosignaling in striated muscle diseases
Zhang, B., Powers, J. D., McCulloch, A. D., & Chi, N. C. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1126111 · Cited by 7
“It is clear that nuclear morphology and deformation play an important role in regulating gene expression in many different cell types (Thomas et al., 2002; Kalukula et al., 2022).”
BackgroundMaintenance of subsynaptic myonuclei number is not driven by neural input
Ruiz, L. P., Macpherson, P. C. D., & Brooks, S. V. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1266950 · Cited by 7
Mechanical forces and the 3D genome
Shivashankar, G. V. (2023) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2023.102728 · Cited by 7
Zhu, H., Miao, R., Wang, J., & Lin, M. (2024) · Mechanobiology in Medicine · doi:10.1016/j.mbm.2024.100040 · Cited by 8
“Nuclear deformation in response to external mechanical stimuli can affect gene expression and signaling pathways [12,13].”
Biophysical determinants of nuclear shape and mechanics and their implications for genome integrity
Hervé, S., & Miroshnikova, Y. A. (2024) · Current Opinion in Biomedical Engineering · doi:10.1016/j.cobme.2024.100521 · Cited by 7
Wrinkling–dewrinkling transitions in stretched soft spherical shells
Hao, Y. A., Li, B., Feng, X., & Gao, H. (2024) · International Journal of Solids and Structures · doi:10.1016/j.ijsolstr.2024.112773 · Cited by 7
Verde, G. L., Artiola, V., Pugliese, M., Commara, M. L., Arrichiello, C., Muto, P., Netti, P. A., Fusco, S., & Panzetta, V. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.969004 · Cited by 8
“A vast literature indicates the key role of nuclear deformability in mediating changes in YAP localization (Elosegui-Artola et al., 2017; Kalukula et al., 2022; Maremonti et al., 2022).”
BackgroundMicrocurvature landscapes induce neural stem cell polarity and enhance neural differentiation
Yuen, H. Y., Yip, W. S., To, S., & Zhao, X. (2023) · Bio-Design and Manufacturing · doi:10.1007/s42242-023-00243-5 · Cited by 7
Actin and CDC-42 contribute to nuclear migration through constricted spaces in C. elegans
Ho, J., Guerrero, L. A., Libuda, D. E., Luxton, G. W. G., & Starr, D. A. (2023) · Development · doi:10.1242/dev.202115 · Cited by 5
Sabri, E., & Brosseau, C. (2023) · Bioelectrochemistry · doi:10.1016/j.bioelechem.2023.108583 · Cited by 7
Zuela-Sopilniak, N., Morival, J. L. P., Ntekas, I., Elpers, M. A., Agarwal, R., Henretta, S. J., Odell, J. D., Vlaminck, I. D., & Lammerding, J. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.06.11.598511 · Cited by 8
“Indeed, despite the transient nature of NE rupture 11,66,67 , we captured these events through co-staining for the cardiomyocyte marker PCM1, RTN4 (representing CM3/CM5 populations), and BAF (representing nuclei with NE rupture) in cKO hearts.”
Self-citationAmphipathic helices sense the inner nuclear membrane environment through lipid packing defectsPreprint
Lee, S., Roux, A. L., Mors, M., Vanni, S., Roca‐Cusachs, P., & Bahmanyar, S. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.11.14.623600 · Cited by 8
Odell, J., Tang, Y., Ambekar, Y. S., Kidiyoor, G. R., Saadi, H., Woodworth, G. F., Holt, L. J., Scarcelli, G., Yu, H., & Lammerding, J. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.07.22.666133 · Cited by 7
Self-citationPhysical effects of 3-D microenvironments on confined cell behaviors
Lan, B.-Q., Wang, Y., Yu, S., Liu, W., & Liu, Y. (2024) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00288.2024 · Cited by 6
Epithelial cell shape changes contribute to regulation of ureteric bud branching morphogenesis
Kurtzeborn, K., Iaroshenko, V., Zárybnický, T., Koivula, J., Anttonen, H., Mäkelä, O., Bridgewater, D. J., Krishnan, R., Chen, P., & Kuure, S. (2025) · FEBS Journal · doi:10.1111/febs.70156 · Cited by 6
“Emerging data indicate that changes in cell adhesion are intimately coupled with nuclear morphology and structure [51,52].”
Mauro, F., Natale, C. F., Panzetta, V., Mollo, V., & Netti, P. A. (2025) · Biomaterials · doi:10.1016/j.biomaterials.2025.123512 · Cited by 6
Jeong, B., Yoon, J., Ahn, J., Lee, B., Park, S., Kim, J.-H., Bayarkhangai, B., Kim, Y., Lee, S., Knowles, J. C., et al. (2025) · Advanced Functional Materials · doi:10.1002/adfm.202503422 · Cited by 6
Shi, Y., Yue, J., Wang, Z., He, S., & Sa, G. (2025) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2025.152524 · Cited by 6
Heterogeneity as a feature: unraveling chromatin’s role in nuclear mechanics
Rodenburg, W. S., Strom, A. R., & Eeftens, J. M. (2025) · Nucleus · doi:10.1080/19491034.2025.2545037 · Cited by 6
“These mechanical deformations can propagate to the nucleus, causing it to deform [1,2].”
Sun, L., Xie, Y., Zuo, Z., Liu, J., Yang, J., Ali, I., Peng, Q., & 邱, 菊. (2025) · Biomaterials Research · doi:10.34133/bmr.0256 · Cited by 7
“…are contingent upon alterations in chromatin structure and gene transcription, with the influence of extracellular matrix forces and cytoskeletal dynamics depending on nuclear deformation mediated by the linker of nucleoskeleton and cytoskeleton complex and nuclear cytoskeleton [ 4 , 5 ].”
Increased substrate stiffness disrupts nuclear-cytoskeletal mechanical coupling in senescent cells
Molina, M. S., Brauer, E., Günther, R., Diederich, S., & Petersen, A. (2025) · Materials Today Bio · doi:10.1016/j.mtbio.2025.102472 · Cited by 7
“Nuclear mechano-adaptation relies on a dynamic balance between cytoskeletal forces and nuclear mechanical properties [50].”
Biomechanics and mechanobiology of the cell nucleus
Wei, F., Liao, Y., Wang, A., Zhang, X., Chen, X., Ma, C.-Y., Li, N., Chen, J., & Long, M. (2025) · Med-X · doi:10.1007/s44258-025-00063-5 · Cited by 7
“Nuclear deformation plays a significant role in important cellular functions, including the muscle contraction, the cell migration, and the pathogenesis of human diseases [9].”
Renkawitz, J., Yesin, A., Kroll, J., Cabral, A. T., D’Annunzio, S., & Thiam, H. R. (2026) · Nucleus · doi:10.1080/19491034.2025.2590843 · Cited by 8
“Nuclear mechanotransduction, which is the study of how forces are transmitted from the extracellular space, the cytoskeleton and the LINC complex to the nucleus, has been extensively reviewed elsewhere [4,138,139].”
InfluentialA Microfluidic Perfusion Culture Setup to Investigate Cell Migration in 3D Constrictions
Geiger, M., Marsico, P., Pensold, D., Weßling, M., Zimmer‐Bensch, G., & Linkhorst, J. (2024) · Advanced Materials Technologies · doi:10.1002/admt.202301535 · Cited by 6
P300 Modulates Endothelial Mechanotransduction of Fluid Shear Stress
Whitworth, C. P., Aw, W. Y., Doherty, E. L., Handler, C., Ambekar, Y. S., Sawhney, A., Scarcelli, G., & Polacheck, W. J. (2024) · Cellular and Molecular Bioengineering · doi:10.1007/s12195-024-00805-2 · Cited by 6
“On the other hand, aberrant compliance can also have detrimental effects, as it makes nuclei more prone to rupture [53].”
Mechanotransduction of the vasculature in Hutchinson-Gilford Progeria Syndrome
Shores, K. L., & Truskey, G. A. (2024) · Frontiers in Physiology · doi:10.3389/fphys.2024.1464678 · Cited by 5
Alyafeai, E., Qaed, E., Al-mashriqi, H. S., Al‐Maamari, A., Almansory, A. H., Futini, F. A., Sultan, M., & Tang, Z. (2024) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2024.111883 · Cited by 10
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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