Rapid unloading experiments from Ttn112-158 muscles

Evidence suggests that the giant muscle protein, titin, functions as a
tunable spring in active muscle. However, the mechanisms for increasing
titin stiffness with activation are not well understood. Previous studies
have suggested that during muscle activation, titin binds to actin which
engages the PEVK region of titin thereby increasing titin stiffness. In
this study, we investigated the role of PEVK titin in active muscle
stiffness during rapid unloading. We measured elastic recoil of active and
passive soleus muscles from Ttn112-158 mice characterized by a 75%
deletion of PEVK titin and increased passive stiffness. We hypothesized
that activated Ttn112-158 muscles are stiffer than wild-type muscles as a
result of the increased stiffness of PEVK titin. Using a servomotor force
lever, we compared the stress-strain relationships of elastic elements in
active and passive muscles during rapid unloading and quantified the
change in stiffness upon activation. The results show that the elastic
modulus of Ttn112-158 muscles increased with activation. However, elastic
elements developed force at 7% longer lengths and exhibited 50% lower
active stiffness in Ttn112-158 soleus muscles than wild-type muscles.
Thus, despite having a shorter, stiffer PEVK segment, during rapid
unloading, Ttn112-158 soleus muscles exhibited reduced active stiffness
compared to wild-type soleus muscles. These results are consistent with
the idea that PEVK titin contributes to active muscle stiffness, however,
the reduction in active stiffness of Ttn112-158 muscles suggests that
other mechanisms compensate for the increased PEVK stiffness.