Titin force in muscle cells alters lattice order, thick and thin filament protein formation.
Anthony L HesselWeikang MaNicole MazaraPaige E RiceDevin NissenHenry GongMichel N KuehnThomas C IrvingWolfgang A LinkePublished in: Proceedings of the National Academy of Sciences of the United States of America (2022)
Skeletal muscle force production is increased at longer compared to shorter muscle lengths because of length-dependent priming of thick filament proteins in the contractile unit before contraction. Using small-angle X-ray diffraction in combination with a mouse model that specifically cleaves the stretch-sensitive titin protein, we found that titin cleavage diminished the length-dependent priming of the thick filament. Strikingly, a titin-sensitive, length-dependent priming was also present in thin filaments, which seems only possible via bridge proteins between thick and thin filaments in resting muscle, potentially myosin-binding protein C. We further show that these bridges can be forcibly ruptured via high-speed stretches. Our results advance a paradigm shift to the fundamental regulation of length-dependent priming, with titin as the key driver.
Keyphrases
- skeletal muscle
- binding protein
- high speed
- mouse model
- high resolution
- insulin resistance
- single molecule
- atomic force microscopy
- heart rate variability
- magnetic resonance
- computed tomography
- smooth muscle
- protein protein
- metabolic syndrome
- amino acid
- subarachnoid hemorrhage
- cell death
- small molecule
- oxidative stress
- brain injury