Mechanobiological landscape of muscle stem cells

Skeletal muscle is distinguished by its remarkable regenerative capacity and mechanical resilience. Continuously challenged by mechanical stress, it adapts to increased load through hypertrophy but undergoes atrophy when mechanical stress is reduced. This regenerative plasticity depends on tissue-resident muscle stem cells (satellite cells; MuSCs), which orchestrate regeneration following injury. Recent studies reveal that change in the MuSCs microenvironment (niche) regulate their regenerative capacity, with particular attention being given to the mechanisms of mechanosensation. In this review, we summarize our current knowledge of the mechanosensory mechanisms through which MuSCs respond to mechanical perturbations in regenerating myofibers. We highlight recent advances in mechanosensitive receptors, including ion channels, and the downstream mechano-signaling pathways that shape MuSC fate. Finally, we discuss future directions in the field, emphasizing emerging biochemical and biomedical technologies that advance the study of MuSC mechanobiology.