Molecular and supra-molecular control of the dynamics of muscle relaxation following action potential stimulation

We will exploit the unique capability of ID02 to measure µm- to nm- scale X-ray reflections with millisecond time resolution to determine both the molecular and supra-molecular mechanisms that control the dynamics of relaxation of intact skeletal muscles following single action potential stimulation in near-physiological conditions that mimic the performance of the muscle-tendon complex in vivo. On the molecular scale, we will measure structural changes in both the thick (myosin-containing) and thin (actin-containing) filaments. On the supra-molecular scale, we will characterize the inter-sarcomere dynamics that limit the rate of relaxation in vivo, and relate those changes in sarcomere length to simultaneous conformational changes in the thick and thin filaments. The results will underpin the development of new therapeutics for muscle weakness.