Contractility of cardiac and skeletal muscle tissue increases with environmental stiffness

The mechanical interplay between contractility and mechanosensing in striated muscles is of fundamental importance for tissue morphogenesis, load adaptation, and disease progression, but remains poorly understood. In this study, we investigate the dependence of contractile force generation of cardiac and skeletal muscle on environmental stiffness. Using in vitro engineered muscle micro-tissues that are attached to flexible elastic pillars, we vary the stiffness of the microenvironment over three orders of magnitude and study its effect on contractility. We find that the active contractile force upon electrical stimulation of both cardiac and skeletal micro-tissues increases with environmental stiffness according to a strong power-law relationship. To explore the role of adhesion-mediated mechanotransduction processes, we deplete the focal adhesion protein β-parvin in skeletal micro-tissues. This reduces the absolute contractile force but leaves the mechanoresponsiveness unaffected. Our findings highlight the influence of external stiffness on the adaptive behavior of muscle tissue and shed light on the complex mechanoadaptation processes in striated muscle.