Researchers in Japan have developed a protein-based gel that mimics the softness and microgrooves of natural skeletal muscle, allowing precursor cells to mature into true slow-twitch fibers in the lab for the first time. These endurance-oriented muscle cells are critical for posture, glucose metabolism, and combating age-related decline. The advance, published 8 August 2025 in Scientific Reports (DOI: 10.1038/s41598-025-12744-7), paves the way for regenerative therapies, drug screening, and transplantable muscle tissue.
Slow-twitch (type I) fibers rely on oxidative metabolism, express high levels of MYH7, GLUT4, and myoglobin, and are regulated by PGC-1α. Replicating them outside the body has eluded scientists due to mismatched mechanical cues. “Conventional plastic or glass substrates are orders of magnitude too stiff,” said lead researcher Dr. Mitsumasa Taguchi of the Takasaki Institute for Advanced Quantum Science at Japan’s National Institutes for Quantum Science and Technology (QST).
Radiation-Crosslinked Gelatin with Tunable Elasticity
Using gamma-ray-induced crosslinking, the team created gelatin hydrogels with elastic moduli from 10 kPa to 100 kPa—matching the softness of living muscle. Optional 10-µm-wide microgrooves were added via molding. When mouse myoblasts (C2C12) were cultured on the softest (10 kPa) gel:
- Slow-twitch genes (MYH7, MYH2) were strongly upregulated.
- Metabolic markers (GLUT4, myoglobin) and PGC-1α increased significantly.
- Cells aligned into fibrous, muscle-like bundles—enhanced further by microgrooves.
“Elasticity drives fiber-type fate; topography guides architecture,” Taguchi summarized.
Clinical and Research Horizons
The biocompatible, biodegradable gel could serve as:
- Scaffolds for regenerating damaged muscle in sarcopenia or dystrophy patients.
- Drug-testing platforms to screen compounds that preserve slow-twitch function.
- Transplantable tissue patches to restore metabolic health in diabetes or obesity.
“This technology could extend healthy lifespan and enable personalized muscle repair,” Taguchi said.
Funding and IP
Supported by Japan Science and Technology Agency (JST A-STEP, ACT-X), the Acquisition, Technology and Logistics Agency, and JSPS KAKENHI grants. A core patent on the crosslinked gelatin (JP-7414224) is registered; a second application covering the muscle-culture system is pending.
Scientific Reports
DOI
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