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 (Coresponding Author), Yongsung Hwang (Coresponding Author)

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)
7 Downloads (Pure)

Abstract

The cell–cell/cell–matrix interactions between myoblasts and their extracellular microenvi-ronment 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, observ-ing 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.

Original languageEnglish
Article number2488
Pages (from-to)1-19
Number of pages19
JournalInternational Journal of Molecular Sciences
Volume22
Issue number5
DOIs
Publication statusPublished - Mar 2021
Externally publishedYes

Keywords*

  • Focal adhesion kinase (FAK)
  • Fusion
  • Myoblast
  • Myogenic differ-entiation
  • Poly(sodium-4-styrenesulfonate)
  • Synthetic mimic of heparin

Field of Science*

  • 1.4 Chemical sciences
  • 2.5 Materials engineering
  • 2.6 Medical engineering

Publication Type*

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

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