The regenerative capacity of skeletal muscle is largely attributed to resident muscle stem cells (MuSCs), which exist mostly in a quiescent state and in the event of tissue damage become activated and differentiate into proliferative myoblasts. MuSCs mechanosense the stiffness of their environment, which is influenced by extracellular matrix (ECM) composition; however, how myoblast proliferation and differentiation are affected by ECM composition and stiffness requires further investigation. In this work (Nguyen et al., 2024), Gilbert and colleagues investigate how ECM ligands and substrate stiffness influence cellular responses of primary human myoblasts. Here, they grow myoblasts on polyacrylamide gels of differing stiffness tethered with either collagen 1, laminin or fibronectin, and find that fibronectin has a more pronounced impact on myoblast behaviour, including proliferation, morphology and contractility. Softer substrates are also associated with increased nuclear wrinkling, which is indicative of decreased contractility. Furthermore, the authors discover that myoblast proliferation is linked to contractility, as nuclear wrinkling can predict levels of the proliferation marker Ki67, and manipulating contractility modulates nuclear wrinkling and myoblast proliferation. Taken together, these findings provide insights into how ECM composition and stiffness can influence myoblast contractility-dependent proliferation, which is relevant to ECM remodelling during regeneration, ageing and disease.
