Contractile and metabolic properties of engineered skeletal muscle derived from slow and fast phenotype mouse muscle.

Abstract

Satellite cells derived from fast and slow muscles have been shown to adopt contractile and metabolic properties of their parent muscle. Mouse muscle shows less distinctive fiber-type profiles than rat or rabbit muscle. Therefore, in this study we sought to determine whether three-dimensional muscle constructs engineered from slow soleus (SOL) and fast tibialis anterior (TA) from mice would adopt the contractile and metabolic properties of their parent muscle. Time-to-peak tension (TPT) and half-relaxation time (1/2RT) was significantly slower in SOL constructs. In agreement with TPT, TA constructs contained significantly higher levels of fast myosin heavy chain (MHC) and fast troponin C, I, and T isoforms. Fast SERCA protein, both slow and fast calsequestrin isoforms and parvalbumin were found at higher levels in TA constructs. SOL constructs were more fatigue resistant and contained higher levels of the mitochondrial proteins SDH and ATP synthase and the fatty acid transporter CPT-1. SOL constructs contained lower levels of the glycolytic enzyme phosphofructokinase but higher levels of the β-oxidation enzymes LCAD and VLCAD suggesting greater fat oxidation. Despite no changes in PGC-1α protein, SOL constructs contained higher levels of SIRT1 and PRC. TA constructs contained higher levels of the slow-fiber program repressor SOX6 and the six transcriptional complex (STC) proteins Eya1 and Six4 which may underlie the higher in fast-fiber and lower slow-fiber program proteins. Overall, we have found that muscles engineered from predominantly slow and fast mouse muscle retain contractile and metabolic properties of their native muscle.