Key result
The high-throughput X-ray diffraction setup at the LiX beamline demonstrated that fMyBP-C cleavage expanded the actomyosin lattice, and addition of mavacamten partially reversed these effects.
Why the study?
Methodological advances were developed at the LiX beamline to support small-angle X-ray scattering experiments on muscle tissues and expand user capacity for research into sarcomeric proteins and myopathies.
The LiX beamline provides high-throughput X-ray diffraction capabilities for muscle tissues, successfully demonstrating that mavacamten partially reverses the structural sarcomeric changes induced by fMyBP-C cleavage in a preclinical model.
We report on recent methodological advances at the Life Science X-ray Scattering (LiX) beamline of the National Synchrotron Light Source II (NSLS-II) to support small-angle X-ray scattering experiments on skeletal and cardiac muscle tissues. These experiments have been routinely performed at the BioCAT beamline of the Advanced Photon Source (APS) over the past two decades to measure sarcomeric protein organization within healthy and diseased muscle tissues and provide direct molecular evidence for their functional roles and dynamics. Many recent advances in our understanding of sarcomeric proteins relied on diffraction data and include, as examples, MyBP-C, crossbridge SRX/DRX states, and titin. With LiX now available for muscle experimentation, more muscle users can be supported which will speed up research of sarcomeric proteins, muscle biomechanics, and skeletal and cardiac myopathies. LiX explicitly focuses on high-throughput muscle diffraction with rapid sample turnover and semi-automated data processing. These operations have been tested and validated on skeletal and cardiac tissues sourced from both humans and multiple animal models including pig, rat, mouse, and zebrafish.
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Nguyen et al. (2026) studied this question. fMyBP-C cleavage via TEV protease followed by mavacamten vs. Control (relaxing solution without compounds) was evaluated on Shifts in muscle diffraction values (lattice spacing d10, intensity ratio I1,1/I1,0, and M3 spacing). The high-throughput X-ray diffraction setup at the LiX beamline demonstrated that fMyBP-C cleavage expanded the actomyosin lattice, and addition of mavacamten partially reversed these effects.
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