Contractility of striated muscle tissue increases with environmental stiffness according to a power-law relationship

Abstract The interplay between contractility and mechanosensing in striated muscle is important for tissue morphogenesis, load adaptation, and disease progression, but remains poorly understood. Here, we investigate how contractile force generation in neonatal rat cardiac and C2C12 mouse skeletal muscle micro-tissues depends on environmental stiffness. Micro-tissues self-assemble and mature over one week between flexible elastic pillars with adjustable stiffness that we vary over three orders of magnitude. Contractile forces are measured from pillar deflections and are decomposed into static baseline and transient active forces in response to electrical stimulation. After 3–5 days of maturation, we find that the active, but not static, force of both cardiac and skeletal micro-tissues increases with environmental stiffness according to a strong power-law relationship, indicating a pronounced mechanoresponsiveness. Depleting the focal adhesion protein β-parvin in skeletal muscle miscro-tissues reduces absolute contractile force but does not affect mechanoresponsiveness. Our findings highlight the influence of external stiffness in striated muscle during development.