Regulation of skeletal myotube formation and alignment by nanotopographically controlled cell-secreted extracellular matrix

Alex Jiao, Charles T. Moerk, Nisa Penland, Mikael Perla, Jinsung Kim, Alec S.T. Smith, Charles E. Murry, Deok Ho Kim

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Skeletal muscle has a well-organized tissue structure comprised of aligned myofibers and an encasing extracellular matrix (ECM) sheath or lamina, within which reside satellite cells. We hypothesize that the organization of skeletal muscle tissues in culture can affect both the structure of the deposited ECM and the differentiation potential of developing myotubes. Furthermore, we posit that cellular and ECM cues can be a strong determinant of myoblast fusion and morphology in 3D tissue culture environments. To test these, we utilized a thermoresponsive nanofabricated substratum to engineer anisotropic sheets of myoblasts which could then be transferred and stacked into multilayered tissues. Within such engineered tissues, we found that myoblasts rapidly sense topography and deposit structurally organized ECM proteins. Furthermore, the initial tissue structure was found to exert significant control over myoblast fusion and eventual myotube organization. These results highlight the importance of ECM structure on myoblast fusion and organization, and provide insights into substrate-mediated control of myotube formation in the development of novel, more effective, engineered skeletal muscle tissues.

Original languageEnglish (US)
Pages (from-to)1543-1551
Number of pages9
JournalJournal of Biomedical Materials Research - Part A
Volume106
Issue number6
DOIs
StatePublished - Jun 2018
Externally publishedYes

Keywords

  • extracellular matrix
  • myotube
  • nanotopography
  • skeletal muscle
  • thermoresponsive

ASJC Scopus subject areas

  • Ceramics and Composites
  • Biomaterials
  • Biomedical Engineering
  • Metals and Alloys

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