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Nanomechanical Analysis of Extracellular Matrix and Cells in Multicellular Spheroids.
Vyas, Varun; Solomon, Melani; D'Souza, Gerard G M; Huey, Bryan D.
Afiliación
  • Vyas V; Materials Science and Engineering Department, University of Connecticut, 97 North Eagleville Road, Unit 3136, Storrs, CT 06269-3136 USA.
  • Solomon M; Pharmaceutical Sciences, Massachusetts College of Pharmacy & Health Sciences, Boston, MA 02115 USA.
  • D'Souza GGM; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD 21205 USA.
  • Huey BD; Pharmaceutical Sciences, Massachusetts College of Pharmacy & Health Sciences, Boston, MA 02115 USA.
Cell Mol Bioeng ; 12(3): 203-214, 2019 Jun.
Article en En | MEDLINE | ID: mdl-31719910
INTRODUCTION: Over the last decade, atomic force microscopy (AFM) has played an important role in understanding nanomechanical properties of various cancer cell lines. This study is focused on Lewis lung carcinoma cell tumours as 3D multicellular spheroid (MS). Not much is know about the mechanical properties of the cells and the surrounding extracellular matrix (ECM) in rapidly growing tumours. METHODS: Depth-dependent indentation measurements were conducted with the AFM. Force-vs.-indentation curves were used to create stiffness profiles as a function of depth. Here studies were focused on the outer most layer, i.e., proliferation zone of the spheroid. RESULTS: Both surface and sub-surface stiffness profiles of MS were created. This study revealed three nanomechanical topographies, Type A-high modulus due to collagen fibers, Type B-high stiffness at cell membrane and ECM interface and Type C-increased modulus due to cell lying deep inside matrix at a depth of 1.35 µm. Both Type and Type-B topographies result from collagen-based structures in ECM. CONCLUSION: This study has first time revealed mechanical constitution of an MS. Depth-dependent indentation studies have the revealed role of various molecular and cellular components responsible for providing mechanical stability to MS. Nanomechanical heterogeneities revealed in this investigation can shed new light in developing correct dosage regime for collagenase treatment of tumours and designing better controlled artificial extracellular matrix systems for replicating tissue growth in-vitro.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Cell Mol Bioeng Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Cell Mol Bioeng Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos