ArticleProceedings of the National Academy of Sciences of the United States of America2002
Engineering gene expression and protein synthesis by modulation of nuclear shape.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 189 papers.
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Who cites it
189 citing papers in PubMed, 484 citations in OpenAlex.
- Nuclear and cellular alignment of primary corneal epithelial cells on topography.Journal of biomedical materials research. Part A · 2013Trial
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- A Computational Model of Mechanical Stretching of Cultured Cells on a Flexible Membrane.Research square · 2026Article
- Periodic confined cell migration drives partially reversible chromatin reorganization in cancer cell lines.Communications biology · 2026Article
- Prognostic value of nuclear features based on tumor-associated collagen signatures in breast cancer.NPJ breast cancer · 2025Article
- Cardiomyocyte Nuclear Pleomorphism in a Mouse Model of Inherited Hypertrophic Cardiomyopathy.Journal of cardiovascular development and disease · 2025Article
- Microtubules and mechanosensing: key players in endothelial responses to mechanical stimuli.Cellular and molecular life sciences : CMLS · 2025Review
- Bionic Nanostructures Create Mechanical Signals to Mediate the Composite Structural Bone Regeneration Through Multi-System Regulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Proteomic analysis of liver fibrosis reveals EFEMP1 as a new modulator of focal adhesion and migration of hepatic stellate cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
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- Biphasic regulation of epigenetic state by matrix stiffness during cell reprogramming.Science advances · 2024Article
- Effects of polydimethylsiloxane membrane surface treatments on human uterine smooth muscle cell strain response.Bioactive materials · 2024Article
- Engineered three-dimensional bioactive scaffold for enhanced bone regeneration through modulating transplanted adipose derived mesenchymal stem cell and stimulating angiogenesis.Frontiers in bioengineering and biotechnology · 2024Article
- Embryo movement is required for limb tendon maturation.Frontiers in cell and developmental biology · 2024Article
- Recombinant lysyl oxidase effects on embryonic tendon cell phenotype and behavior.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2023Article
- Cerebral organoids as an in vitro model to study autism spectrum disorders.Gene therapy · 2023Review
- Macromolecular crowding regulates matrix composition and gene expression in human gingival fibroblast cultures.Scientific reports · 2023Article
129 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
The current understanding of the relationships between cell shape, intracellular forces and signaling, nuclear shape and organization, and gene expression is in its infancy. Here we introduce a method for investigating gene-specific responses in individual cells with controlled nuclear shape and projected area. The shape of the nuclei of primary osteogenic cells were controlled on microfabricated substrata with regiospecific chemistry by confining attachment and spreading of isolated cells on adhesive islands. Gene expression and protein synthesis were altered by changing nuclear shape. Collagen I synthesis correlated directly with cell shape and nuclear shape index (NSI), where intermediate values of nuclear distension (6 < NSI < 8) promoted maximum synthesis. Osteocalcin mRNA, a bone-specific differentiation marker, was observed intracellularly by using reverse transcription in situ PCR at 4 days in cells constrained by the pattern and not detected in unconstrained cells of similar projected area, but different NSI. Our data supports the concept of gene expression and protein synthesis based on optimal distortion of the nucleus, possibly altering transcription factor affinity for DNA, transport to the nucleus, or nuclear matrix organization. The combination of microfabricated surfaces, reverse transcription in situ PCR, and NSI measurement is an excellent system to study how transcription factors, the nuclear matrix, and the cytoskeleton interact to control gene expression and may be useful for studying a wide variety of other cell shape/gene expression relationships.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.