Nanotopography-induced changes in focal adhesions, cytoskeletal organization, and mechanical properties of human mesenchymal stem cells
Open accessAbstract
The growth of stem cells can be modulated by physical factors such as extracellular matrix nanotopography. We hypothesize that nanotopography modulates cell behavior by changing the integrin clustering and focal adhesion (FA) assembly, leading to changes in cytoskeletal organization and cell mechanical properties. Human mesenchymal stem cells (hMSCs) cultured on 350 nm gratings of tissue-culture polystyrene (TCPS) and polydimethylsiloxane (PDMS) showed decreased expression of integrin subunits alpha2, alpha , alpha V, beta2, beta 3 and beta 4 compared to the unpatterned controls. On gratings, the elongated hMSCs exhibited an aligned actin cytoskeleton, while on unpatterned controls, spreading cells showed a random but denser actin cytoskeleton network. Expression of cytoskeleton and FA components was also altered by the nanotopography as reflected in the mechanical properties measured by atomic force microscopy (AFM) indentation. On the rigid TCPS, hMSCs on gratings exhibited lower instantaneous and equilibrium Young's moduli and apparent viscosity. On the softer PDMS, the effects of nanotopography were not significant. However, hMSCs cultured on PDMS showed lower cell mechanical properties than those on TCPS, regardless of topography. These suggest that both nanotopography and substrate stiffness could be important in determining mechanical properties, while nanotopography may be more dominant in determining the organization of the cytoskeleton and FAs.
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Increasing stem cell evidence indicates that substrate physical features direct differentiation via adhesion signaling and cytoskeletal changes.
“a growing body of evidence in the stem cell field suggest that physical features on the culture substrate regulate differentiation through changes adhesion signaling and cytoskeletal organization.28-31”
From Micro- and Nanopatterned Topographical Cues for Regulating Macrophage Cell Shape and Phenotype (2015) · cites this paper as [29]
Grooved substrates alter integrin expression and FAK phosphorylation.
“Grooved substrates also lead to changes in integrin expression and focal adhesion kinase (FAK) phosphorylation.29”
From Micro- and Nanopatterned Topographical Cues for Regulating Macrophage Cell Shape and Phenotype (2015) · cites this paper as [29]
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- Authors
- Yim, E. K. F., Darling, E. M., Kulangara, K., Guilak, F., & Leong, K. W.
- Affiliations
- Duke University (US)
- Corresponding author
- Yim, Evelyn K.F.
- Leong, Kam W.
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2010-02
- Volume
- 31
- Issue
- 6
- Pages
- 1299-1306
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC2813896
- OpenAlex
- W2154421213
- Cited by
- 712
- References
- 40
- Citations by year
- 2026: 15 · 2025: 28 · 2024: 16 · 2023: 25 · 2022: 36 · 2021: 39 · 2020: 40 · 2019: 45 · 2018: 54 · 2017: 77 · 2016: 50 · 2015: 75 · 2014: 64 · 2013: 53 · 2012: 49
- FWCI
- 13.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DukeSpace (Duke University) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institutes of Health (AG15768, AR48182, AR48852, AR50245, AR53448, HL83008)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (PBEL2-115950)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Physical Sciences › Physics and Astronomy › Atomic and Molecular Physics, and Optics › Force Microscopy Techniques and Applications
- Keywords
- nanotopography, human mesenchymal stem cells, focal adhesions, integrin clustering, cell mechanical properties, substrate stiffness, polydimethylsiloxane, tissue culture polystyrene, Young's modulus, cell adhesion
- MeSH terms
- Cell Adhesion, Cells, Cultured, Cytoskeleton, Humans, Materials Testing, Surface Properties, Cell Polarity, Compressive Strength, Focal Adhesions, Nanostructures, Elastic Modulus, Mesenchymal Stem Cells
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