Titin force in muscle cells alters lattice order, thick and thin filament protein formation

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.

Automated summary

This study found that skeletal muscle force production increases with longer muscle lengths due to length-dependent priming of thick filament proteins in the muscle unit before contraction. The research also discovered that bridge proteins between thick and thin filaments, potentially myosin-binding protein C, play a role in the length-dependent priming of thin filaments. These bridges can be forcibly ruptured via high-speed stretches.