International Journal of Molecular Sciences (Mar 2021)

Heparin-Mimicking Polymer-Based In Vitro Platform Recapitulates In Vivo Muscle Atrophy Phenotypes

  • Hyunbum Kim,
  • Ji Hoon Jeong,
  • Mona Fendereski,
  • Hyo-Shin Lee,
  • Da Yeon Kang,
  • Sung Sik Hur,
  • Jhaleh Amirian,
  • Yunhye Kim,
  • Nghia Thi Pham,
  • Nayoung Suh,
  • Nathaniel Suk-Yeon Hwang,
  • Seongho Ryu,
  • Jeong Kyo Yoon,
  • Yongsung Hwang

DOI
https://doi.org/10.3390/ijms22052488
Journal volume & issue
Vol. 22, no. 5
p. 2488

Abstract

Read online

The cell–cell/cell–matrix interactions between myoblasts and their extracellular microenvironment have been shown to play a crucial role in the regulation of in vitro myogenic differentiation and in vivo skeletal muscle regeneration. In this study, by harnessing the heparin-mimicking polymer, poly(sodium-4-styrenesulfonate) (PSS), which has a negatively charged surface, we engineered an in vitro cell culture platform for the purpose of recapitulating in vivo muscle atrophy-like phenotypes. Our initial findings showed that heparin-mimicking moieties inhibited the fusion of mononucleated myoblasts into multinucleated myotubes, as indicated by the decreased gene and protein expression levels of myogenic factors, myotube fusion-related markers, and focal adhesion kinase (FAK). We further elucidated the underlying molecular mechanism via transcriptome analyses, observing that the insulin/PI3K/mTOR and Wnt signaling pathways were significantly downregulated by heparin-mimicking moieties through the inhibition of FAK/Cav3. Taken together, the easy-to-adapt heparin-mimicking polymer-based in vitro cell culture platform could be an attractive platform for potential applications in drug screening, providing clear readouts of changes in insulin/PI3K/mTOR and Wnt signaling pathways.

Keywords