Redox regulation of protein nanomechanics in health and disease: Lessons from titin

The nanomechanics of sarcomeric proteins is a key contributor to the mechanical output of muscle. Among them, titin emerges as a main target for the regulation of the stiffness of striated muscle. In the last years, single-molecule experiments by Atomic Force Microscopy (AFM) have demonstrated that redox posttranslational modifications are strong modulators of the mechanical function of titin. Here, we provide an overview of the recent development of the redox mechanobiology of titin, and suggest avenues of research to better understand how the stiffness of molecules, cells and tissues are modulated by redox signaling in health and disease.