Effects of a titin mutation on negative work during stretch-shortening cycles in skeletal muscles

Negative work occurs in muscles during braking movements such as downhill walking or landing after a jump. When performing negative work during stretch-shortening cycles, viscoelastic structures within muscles store energy during stretch, return a fraction of this energy during shortening and dissipate the remaining energy as heat. Because tendons and extracellular matrix are relatively elastic rather than viscoelastic, energy is mainly dissipated by cross bridges and titin. Recent studies demonstrate that titin stiffness increases in active skeletal muscles, suggesting that titin contributions to negative work may have been underestimated in previous studies. The muscular dystrophy with myositis (mdm) mutation in mice results in a deletion in titin that leads to reduced titin stiffness in active muscle, providing an opportunity to investigate the contribution of titin to negative work in stretch-shortening cycles. Using the work loop technique, extensor digitorum longus and soleus muscles from mdm and wild-type (WT) mice were stimulated during the stretch phase of stretch-shortening cycles to investigate negative work. The results demonstrate that, compared with WT muscles, negative work is reduced in muscles from mdm mice. We suggest that changes in the viscoelastic properties of mdm titin reduce energy storage by muscles during stretch and energy dissipation during shortening. Maximum isometric stress is also reduced in muscles from mdm mice, possibly due to impaired transmission of cross-bridge force, impaired cross-bridge function or both. Functionally, the reduction in negative work could lead to increased muscle damage during eccentric contractions that occur during braking movements.