Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 8, Issue 8, Pages 5082-5092Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.5b10531
Keywords
nanotopography; cell spreading; focal adhesions; nuclear deformation; proliferation; transfection; type I collagen
Funding
- Mary Babb Randolph Cancer Center (MBRCC)
- NIH [P30 GM103488, P20 RR016477]
- MBRCC CoBRE grant [GM103488/RR032138]
- Fortessa S10 grant [OD016165]
- WV InBRE grant [GM103434]
- [NSF CBET 1227766]
- [NSF CBET 1511759]
- [NSF EPS 1003907]
- [NSF EPS-1003907]
- Directorate For Engineering [1511759, 1227766] Funding Source: National Science Foundation
- Directorate For Engineering
- Div Of Chem, Bioeng, Env, & Transp Sys [1434503] Funding Source: National Science Foundation
- Div Of Chem, Bioeng, Env, & Transp Sys [1511759, 1227766] Funding Source: National Science Foundation
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Although nanotopography has been shown to be a potent modulator of cell behavior, it is unclear how the so nanotopographical cue, through focal adhesions, affects the nucleus, eventually influencing cell phenotype and function. Thus, current methods to apply nanotopography to regulate cell behavior are basically empirical. We, herein, engineered nanotopographies of various shapes (gratings and pillars) and dimensions (feature size, spacing and height), and thoroughly investigated cell spreading, focal adhesion organization and nuclear deformation of human primary fibroblasts as the model cell grown on the nanotopographies. We examined the correlation between nuclear deformation and cell functions such as cell proliferation, transfection and extracellular matrix protein type I collagen production. It was found that the nanoscale gratings and pillars could facilitate focal adhesion elongation by providing anchoring sites, and the nanogratings could orient focal adhesions and nuclei along the nanograting direction, depending on not only the feature size but also the spacing of the nanogratings. Compared with continuous nanogratings, discrete nanopillars tended to disrupt the formation and growth of focal adhesions and thus had less profound effects on nuclear deformation. Notably, nuclear volume could be effectively modulated by the height of nanotopography. Further, we demonstrated that cell proliferation, transfection, and type I collagen production were strongly associated with the nuclear volume, indicating that the nucleus serves as a critical mechanosensor for cell regulation. Our study delineated the relationships between focal adhesions, nucleus and cell function and highlighted that the nanotopography could regulate cell phenotype and function by modulating nuclear deformation. This study provides insight into the rational design of nanotopography for new biomaterials and the cell-substrate interfaces of implants and medical devices.
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