title: Mechanical trapping of the nucleus on micropillared surfaces inhibits the proliferation of vascular smooth muscle cells but not cervical cancer HeLa cells.
abstract: The interaction between cells and the extracellular matrix on a topographically patterned surface can result in changes in cell shape and many cellular functions. In the present study, we demonstrated the mechanical deformation and trapping of the intracellular nucleus using polydimethylsiloxane (PDMS)-based microfabricated substrates with an array of micropillars. We investigated the differential effects of nuclear deformation on the proliferation of healthy vascular smooth muscle cells (SMCs) and cervical cancer HeLa cells. Both types of cell spread normally in the space between micropillars and completely invaded the extracellular microstructures, including parts of their cytoplasm and their nuclei. We found that the proliferation of SMCs but not HeLa cells was dramatically inhibited by cultivation on the micropillar substrates, even though remarkable deformation of nuclei was observed in both types of cells. Mechanical testing with an atomic force microscope and a detailed image analysis with confocal microscopy revealed that SMC nuclei had a thicker nuclear lamina and greater expression of lamin A/C than those of HeLa cells, which consequently increased the elastic modulus of the SMC nuclei and their nuclear mechanical resistance against extracellular microstructures. These results indicate that the inhibition of cell proliferation resulted from deformation of the mature lamin structures, which might be exposed to higher internal stress during nuclear deformation. This nuclear stress-induced inhibition of cell proliferation occurred rarely in cancer cells with deformable nuclei.
authors.affiliation: Micro-Nano Biomechanics Laboratory, Department of Intelligent Systems Engineering, Ibaraki University, Nakanarusawa-cho, Hitachi 316-8511, Japan. Electronic address: k-nagaym@mx.ibaraki.ac.jp.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Nagayama
authors.affiliation: Biomechanics Laboratory, Department of Mechanical Engineering, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya 466-8555, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Hamaji
authors.affiliation: Biomechanics Laboratory, Department of Mechanical Engineering, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya 466-8555, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Biomechanics Laboratory, Department of Mechanical Engineering, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya 466-8555, Japan. Electronic address: takeo@nitech.ac.jp.
authors.forename: Takeo
authors.initials: T
authors.lastname: Matsumoto
mesh_terms: D002467:Cell Nucleus / Q000187:drug effects* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003593:Cytoplasm / Q000187:drug effects; D004129:Dimethylpolysiloxanes / Q000494:pharmacology; D055119:Elastic Modulus; D005109:Extracellular Matrix / Q000187:drug effects; D005260:Female; D006367:HeLa Cells; D006801:Humans; D055595:Mechanical Phenomena; D055616:Microtechnology / Q000295:instrumentation*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects*; D002583:Uterine Cervical Neoplasms / Q000473:pathology*
chemical_list: D004129:Dimethylpolysiloxanes; C013830:baysilon
keywords: Atomic force microscopy; Cell biomechanics; Mechanobiology; Microfabrication; Nuclear mechanotransduction