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

Int J Mol Sci. 2021 Mar 2;22(5):2488. doi: 10.3390/ijms22052488.


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: focal adhesion kinase (FAK); fusion; myoblast; myogenic differentiation; poly(sodium-4-styrenesulfonate); synthetic mimic of heparin.

MeSH terms

  • Animals
  • Cell Culture Techniques
  • Cell Differentiation
  • Cell Fusion
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects*
  • Heparin / chemistry*
  • In Vitro Techniques
  • Mice
  • Mice, Inbred C57BL
  • Muscle Development
  • Muscle Fibers, Skeletal / cytology*
  • Muscle Fibers, Skeletal / drug effects
  • Muscle Fibers, Skeletal / metabolism
  • Muscle, Skeletal / cytology*
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • Muscular Atrophy / drug therapy
  • Muscular Atrophy / metabolism
  • Muscular Atrophy / pathology*
  • Myoblasts / cytology*
  • Myoblasts / drug effects
  • Myoblasts / metabolism
  • Phenotype
  • Polymers / administration & dosage*
  • Polymers / chemistry


  • Polymers
  • Heparin