Combined stimuli of elasticity and microgrooves form aligned myotubes that characterize slow twitch muscles

Abstract Skeletal muscles are classified into slow-twitch muscles composed primarily of type I and IIa fibers with high oxidative metabolism, and fast-twitch muscles composed of type IIx and IIb fibers with high glycolytic metabolism. Fiber-type shifts occur during development and aging; however, th...

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Main Authors: Hiroki Hamaguchi, Tomoko G. Oyama, Kotaro Oyama, Yasuko Manabe, Nobuharu L. Fujii, Mitsumasa Taguchi
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-12744-7
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author Hiroki Hamaguchi
Tomoko G. Oyama
Kotaro Oyama
Yasuko Manabe
Nobuharu L. Fujii
Mitsumasa Taguchi
author_facet Hiroki Hamaguchi
Tomoko G. Oyama
Kotaro Oyama
Yasuko Manabe
Nobuharu L. Fujii
Mitsumasa Taguchi
author_sort Hiroki Hamaguchi
collection DOAJ
description Abstract Skeletal muscles are classified into slow-twitch muscles composed primarily of type I and IIa fibers with high oxidative metabolism, and fast-twitch muscles composed of type IIx and IIb fibers with high glycolytic metabolism. Fiber-type shifts occur during development and aging; however, the stimuli that shift these types remain unclear. We analyzed the role of mechanical stimuli in myotube formation and shift to the characteristics of each fiber type using crosslinked gelatin gels with tunable elastic moduli (10–230 kPa) and microgrooves (3–50 µm). C2C12 myotubes on 10 kPa gel increased the expression of marker genes for type I and IIa fibers (MYH7 and MYH2) and oxidative metabolism (GLUT4 and myoglobin) than those on stiffer gels. Upregulation of PGC-1α on soft gel induced a shift toward slow-twitch muscle genetic characteristics. Microgrooves (3–10 µm) enhanced myoblast differentiation and myotube orientation, without affecting the gene expressions characterizing fiber types. This study demonstrated an approach to create highly oriented slow-twitch muscle models by controlling the elasticity and microgrooves.
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spelling doaj-art-5f1540687ef547f7b15bbb535ea3d1b92025-08-20T03:46:07ZengNature PortfolioScientific Reports2045-23222025-08-0115111410.1038/s41598-025-12744-7Combined stimuli of elasticity and microgrooves form aligned myotubes that characterize slow twitch musclesHiroki Hamaguchi0Tomoko G. Oyama1Kotaro Oyama2Yasuko Manabe3Nobuharu L. Fujii4Mitsumasa Taguchi5Takasaki Institute for Advanced Quantum Science, National Institutes for Quantum Science and Technology (QST)Takasaki Institute for Advanced Quantum Science, National Institutes for Quantum Science and Technology (QST)Takasaki Institute for Advanced Quantum Science, National Institutes for Quantum Science and Technology (QST)Department of Health Promotion Sciences, Graduate School of Human Health Sciences, Tokyo Metropolitan UniversityDepartment of Health Promotion Sciences, Graduate School of Human Health Sciences, Tokyo Metropolitan UniversityTakasaki Institute for Advanced Quantum Science, National Institutes for Quantum Science and Technology (QST)Abstract Skeletal muscles are classified into slow-twitch muscles composed primarily of type I and IIa fibers with high oxidative metabolism, and fast-twitch muscles composed of type IIx and IIb fibers with high glycolytic metabolism. Fiber-type shifts occur during development and aging; however, the stimuli that shift these types remain unclear. We analyzed the role of mechanical stimuli in myotube formation and shift to the characteristics of each fiber type using crosslinked gelatin gels with tunable elastic moduli (10–230 kPa) and microgrooves (3–50 µm). C2C12 myotubes on 10 kPa gel increased the expression of marker genes for type I and IIa fibers (MYH7 and MYH2) and oxidative metabolism (GLUT4 and myoglobin) than those on stiffer gels. Upregulation of PGC-1α on soft gel induced a shift toward slow-twitch muscle genetic characteristics. Microgrooves (3–10 µm) enhanced myoblast differentiation and myotube orientation, without affecting the gene expressions characterizing fiber types. This study demonstrated an approach to create highly oriented slow-twitch muscle models by controlling the elasticity and microgrooves.https://doi.org/10.1038/s41598-025-12744-7
spellingShingle Hiroki Hamaguchi
Tomoko G. Oyama
Kotaro Oyama
Yasuko Manabe
Nobuharu L. Fujii
Mitsumasa Taguchi
Combined stimuli of elasticity and microgrooves form aligned myotubes that characterize slow twitch muscles
Scientific Reports
title Combined stimuli of elasticity and microgrooves form aligned myotubes that characterize slow twitch muscles
title_full Combined stimuli of elasticity and microgrooves form aligned myotubes that characterize slow twitch muscles
title_fullStr Combined stimuli of elasticity and microgrooves form aligned myotubes that characterize slow twitch muscles
title_full_unstemmed Combined stimuli of elasticity and microgrooves form aligned myotubes that characterize slow twitch muscles
title_short Combined stimuli of elasticity and microgrooves form aligned myotubes that characterize slow twitch muscles
title_sort combined stimuli of elasticity and microgrooves form aligned myotubes that characterize slow twitch muscles
url https://doi.org/10.1038/s41598-025-12744-7
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