Activation and stretching of myofibrils in the absence of actin-myosin overlap increased muscle force by a factor of 3 to 4 above purely passive forces, a process dependent on titin.
Titin acts as a strong regulator of muscle force based on cross-bridge force-dependent titin-actin interactions, providing a mechanism for sarcomere stability and protection against stretch-induced injuries.
Effect estimate: factor of 3 to 4 increase
For the past half century, the sliding filament-based cross-bridge theory has been the cornerstone of our understanding of how muscles contract. According to this theory, active force can only occur if there is overlap between the contractile filaments, actin and myosin. Otherwise, forces are thought to be caused by passive structural elements and are assumed to vary solely because of the length of the muscle. We observed increases in muscle force by a factor of 3 to 4 above the purely passive forces for activated and stretched myofibrils in the absence of actin-myosin overlap. We show that this dramatic increase in force is crucially dependent on the presence of the structural protein titin, cannot be explained with calcium activation, and is regulated by actin-myosin-based cross-bridge forces before stretching. We conclude from these observations that titin is a strong regulator of muscle force and propose that this regulation is based on cross-bridge force-dependent titin-actin interactions. These results suggest a mechanism for stability of sarcomeres on the "inherently unstable" descending limb of the force-length relationship, and they further provide an explanation for the protection of muscles against stretch-induced muscle injuries.
Leonard et al. (Thu,) reported a other. Activation and stretching of myofibrils in the absence of actin-myosin overlap vs. Purely passive forces was evaluated on Muscle force (factor of 3 to 4 increase). Activation and stretching of myofibrils in the absence of actin-myosin overlap increased muscle force by a factor of 3 to 4 above purely passive forces, a process dependent on titin.