Establishment of a system evaluating the contractile force of electrically stimulated myotubes from wrinkles formed on elastic substrate.

Muscle weakness is detrimental not only to quality of life but also life expectancy. However, effective drugs have still not been developed to improve and prevent muscle weakness associated with aging or diseases. One reason for the delay in drug discovery is that no suitable in vitro screening system has been established to test whether drugs improve muscle strength. Here, we used a specific deformable silicone gel substrate to effectively and sensitively evaluate the contractile force generated by myotubes from wrinkles formed on the substrate. Using this system, it was found that the contractile force generated by an atrophic phenotype of myotubes induced by dexamethasone or cancer cell-conditioned medium treatment significantly decreased while that generated by hypertrophic myotubes induced by insulin-like growth factor-1 significantly increased. Notably, it was found that changes in the index related to contractile force can detect atrophic or hypertrophic phenotypes more sensitively than changes in myotube diameter or myosin heavy chain expression, both commonly used to evaluate myotube function. These results suggest that our proposed system will be an effective tool for assessing the contractile force-related state of myotubes, which are available for the development of drugs to prevent and/or treat muscle weakness.