Differential basal-to-apical accessibility of lamin A/C epitopes in the nuclear lamina regulated by changes in cytoskeletal tension
Open accessAbstract
Nuclear lamins play central roles at the intersection between cytoplasmic signalling and nuclear events. Here, we show that at least two N- and C-terminal lamin epitopes are not accessible at the basal side of the nuclear envelope under environmental conditions known to upregulate cell contractility. The conformational epitope on the Ig-domain of A-type lamins is more buried in the basal than apical nuclear envelope of human mesenchymal stem cells undergoing osteogenesis (but not adipogenesis), and in fibroblasts adhering to rigid (but not soft) polyacrylamide hydrogels. This structural polarization of the lamina is promoted by compressive forces, emerges during cell spreading, and requires lamin A/C multimerization, intact nucleoskeleton-cytoskeleton linkages (LINC), and apical-actin stress-fibre assembly. Notably, the identified Ig-epitope overlaps with emerin, DNA and histone binding sites, and comprises various laminopathy mutation sites. Our findings should help decipher how the physical properties of cellular microenvironments regulate nuclear events.
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Novel 3D cell culture platforms are being created to better mimic in vivo conditions and are sometimes called spheroid or organoid culture.
“To overcome this limitation, novel 3D cell culture platforms are being created to better mimic in vivo conditions and are sometimes called spheroid or organoid culture, as described below (37,61,84,98,117,118).”
From Modeling physiological events in 2D vs. 3D cell culture (2017) · cites this paper as [61]
The Methods section describes cells plated on hydrogels, microposts, and adhesive micro-islands, while ‘Engineered microenvironments regulate LA/C-C epitope accessibility’ examines their effects on the nuclear lamina. Searches for spheroid or organoid culture and for 3D platforms that mimic in vivo conditions found no passage addressing the claim; the paper’s engineered substrates alone do not establish it. (LLM, conf=0.77)
Experimental — accuracy not yet measuredInduced polarity in pseudo-3D models may alter native cell functions in spreading, migrating, and sensing soluble factors and other microenvironmental cues.
“This induced polarity may alter the functions of native cells with regard to spreading, migrating, and sensing soluble factors and other microenvironmental cues (61).”
From Modeling physiological events in 2D vs. 3D cell culture (2017) · cites this paper as [61]
The ‘Engineered microenvironments regulate LA/C-C epitope accessibility’ section reports that substrate properties affect cell spreading and nuclear-lamina polarization. The ‘Physiological implications’ section links that polarization to engineered niches, but neither section says that induced polarity in pseudo-3D models alters native-cell spreading, migration, or sensing of soluble factors and other cues. Searches for pseudo-3D models, migration, and soluble-factor sensing did not locate such a passage. (LLM, conf=0.73)
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- Authors
- Ihalainen, T. O., Aires, L., Herzog, F. A., Schwartlander, R., Moeller, J., & Vogel, V.
- Affiliations
- Tampere University (FI)
- ETH Zurich (CH)
- Venue
- Nature Materials
- Published
- 2015-08-24
- Volume
- 14
- Issue
- 12
- Pages
- 1252-1261
- ISSN
- 1476-1122 (ISSN-L)
- 1476-4660
- PMC
- PMC4655446
- OpenAlex
- W1201251126
- Cited by
- 172
- References
- 52
- Citations by year
- 2026: 8 · 2025: 17 · 2024: 5 · 2023: 21 · 2022: 17 · 2021: 14 · 2020: 17 · 2019: 26 · 2018: 19 · 2017: 13 · 2016: 14
- FWCI
- 6.66
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Materials (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (133122)
- 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
- lamin A/C, nuclear lamina, nuclear envelope, epitope accessibility, cytoskeletal tension, LINC complex, stress fibers, cell contractility, mesenchymal stem cells, bone formation, fibroblasts, polyacrylamide hydrogel, laminopathies, emerin
- MeSH terms
- Biopolymers, Cytoskeleton, Humans, Protein Conformation, Nuclear Lamina, Lamin Type A
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