ArticleNucleus (Austin, Tex.)
Soft substrates normalize nuclear morphology and prevent nuclear rupture in fibroblasts from a laminopathy patient with compound heterozygous LMNA mutations.
Article in Nucleus (Austin, Tex.). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Mechanosensing by the nucleus: From pathways to scaling relationships.The Journal of cell biology · 2017Pooled it
- Variable A-type lamin expression in Merkel cell carcinoma cell lines and its association with nuclear integrity.Scientific reports · 2026Article
- Lamin B1 and LAP2β resist cytoskeletal force to maintain lamin A/C meshwork organization and preserve nuclear integrity.Molecular biology of the cell · 2025Article
- Peripheral heterochromatin tethering is required for chromatin-based nuclear mechanical response.Nucleic acids research · 2025Article
- Attenuated Nuclear Tension Regulates Progerin-Induced Mechanosensitive Nuclear Wrinkling and Chromatin Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Extracellular matrix stiffness in endometrial cancer: driving progression and modulating treatment sensitivity via the ROCK1/YAP1 axis.Cell death & disease · 2025Article
- Extracellular matrix stiffness: mechanisms in tumor progression and therapeutic potential in cancer.Experimental hematology & oncology · 2025Review
- Unveiling the potential of biomechanics in pioneering innovative strategies for cancer therapy.Theranostics · 2025Review
- A high-content screen reveals new regulators of nuclear membrane stability.Scientific reports · 2024Article
- The Role of β-Dystroglycan in Nuclear Dynamics.Cells · 2024Article
- Mechanisms by which barrier-to-autointegration factor regulates dynamics of nucleocytoplasmic leakage and membrane repair following nuclear envelope rupture.bioRxiv : the preprint server for biology · 2023Article
- A high-content screen reveals new regulators of nuclear membrane stability.bioRxiv : the preprint server for biology · 2023Article
- Small lipid droplets are rigid enough to indent a nucleus, dilute the lamina, and cause rupture.The Journal of cell biology · 2023Article
- Gaussian curvature dilutes the nuclear lamina, favoring nuclear rupture, especially at high strain rate.Nucleus (Austin, Tex.) · 2022Article
- The BAF A12T mutation disrupts lamin A/C interaction, impairing robust repair of nuclear envelope ruptures in Nestor-Guillermo progeria syndrome cells.Nucleic acids research · 2022Article
- Sculpting Rupture-Free Nuclear Shapes in Fibrous Environments.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Nuclear mechanoprotection: From tissue atlases as blueprints to distinctive regulation of nuclear lamins.APL bioengineering · 2022Review
- Article
- Super-Resolution Imaging of the A- and B-Type Lamin Networks: A Comparative Study of Different Fluorescence Labeling Procedures.International journal of molecular sciences · 2021Article
- Nuclear membrane ruptures underlie the vascular pathology in a mouse model of Hutchinson-Gilford progeria syndrome.JCI insight · 2021Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Laminopathies, mainly caused by mutations in the LMNA gene, are a group of inherited diseases with a highly variable penetrance; i.e., the disease spectrum in persons with identical LMNA mutations range from symptom-free conditions to severe cardiomyopathy and progeria, leading to early death. LMNA mutations cause nuclear abnormalities and cellular fragility in response to cellular mechanical stress, but the genotype/phenotype correlations in these diseases remain unclear. Consequently, tools such as mutation analysis are not adequate for predicting the course of the disease. Here, we employ growth substrate stiffness to probe nuclear fragility in cultured dermal fibroblasts from a laminopathy patient with compound progeroid syndrome. We show that culturing of these cells on substrates with stiffness higher than 10 kPa results in malformations and even rupture of the nuclei, while culture on a soft substrate (3 kPa) protects the nuclei from morphological alterations and ruptures. No malformations were seen in healthy control cells at any substrate stiffness. In addition, analysis of the actin cytoskeleton organization in this laminopathy cells demonstrates that the onset of nuclear abnormalities correlates to an increase in cytoskeletal tension. Together, these data indicate that culturing of these LMNA mutated cells on substrates with a range of different stiffnesses can be used to probe the degree of nuclear fragility. This assay may be useful in predicting patient-specific phenotypic development and in investigations on the underlying mechanisms of nuclear and cellular fragility in laminopathies.
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