title: Nanotopographical Modulation of Cell Function through Nuclear Deformation.
abstract: Although nanotopography has been shown to be a potent modulator of cell behavior, it is unclear how the 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.
authors: Department of Chemical Engineering, West Virginia University , Morgantown, West Virginia 26506, United States.
authors: Kai
authors: K
authors: Wang
authors: Department of Chemical Engineering, West Virginia University , Morgantown, West Virginia 26506, United States.
authors: Allison
authors: A
authors: Bruce
authors: Department of Chemical Engineering, West Virginia University , Morgantown, West Virginia 26506, United States.
authors: Ryan
authors: R
authors: Mezan
authors: Lane Department of Computer Science and Electrical Engineering, West Virginia University , Morgantown, West Virginia 26506, United States.
authors: Anand
authors: A
authors: Kadiyala
authors: Allergy and Clinical Immunology Branch, National Institute for Occupational Safety and Health , Morgantown, West Virginia 26505, United States.
authors: Liying
authors: L
authors: Wang
authors: Lane Department of Computer Science and Electrical Engineering, West Virginia University , Morgantown, West Virginia 26506, United States.
authors: Jeremy
authors: J
authors: Dawson
authors: Department of Basic Pharmaceutical Sciences, West Virginia University , Morgantown, West Virginia 26506, United States.
authors: Yon
authors: Y
authors: Rojanasakul
authors: Department of Chemical Engineering, West Virginia University , Morgantown, West Virginia 26506, United States.
authors: Yong
authors: Y
authors: Yang
mesh_terms: D002448:Cell Adhesion / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002466:Cell Nucleolus / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D048430:Cell Shape; D048429:Cell Size; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology; D022001:Focal Adhesions / Q000235:genetics*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D036103:Nanotechnology
keywords: cell spreading; focal adhesions; nanotopography; nuclear deformation; proliferation; transfection; type I collagen