Meeting Abstract

P2-21    Active muscle stiffness is reduced during rapid unloading in Ttn ^?112-158 soleus muscles with a deletion to PEVK titin Hurley, K/L*; Bassett, J/R; Monroy, J/A; Claremont Colleges khurley@students.pitzer.edu

Mounting evidence suggests that the muscle protein, titin functions as a tunable spring in active muscle. However, the mechanism for increasing titin stiffness with activation is not fully understood. Previous studies have suggested that during muscle activation, titin binds to actin which engages the PEVK region of titin and increases titin and whole muscle stiffness. In this study, we further investigated the contribution of PEVK titin to active muscle stiffness during rapid unloading. Using a servomotor force lever, we measured elastic recoil of active and passive soleus muscles from the in Ttn ^?112-158 mouse characterized by 75% deletion of PEVK titin and increased passive stiffness. We hypothesized that in Ttn ^?112-158 muscles are actively more stiff than wild type muscles due to the increased stiffness of PEVK titin. 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. Results from wild type muscles showed that the equilibrium length of elastic elements decreased by ~15% and the elastic modulus increased ~2.9 fold with activation. However, contrary to our initial hypothesis, in Ttn ^?112-158soleus muscles, elastic elements developed force at 7% longer lengths and exhibited 50%; lower active stiffness than wild-type muscles. The findings that active in Ttn ^?112-158 muscles are less stiff than wild-type muscles suggest that the current proposed mechanisms for increasing titin stiffness with activation are incomplete. Additional mechanisms likely compensate for the shorter, stiffer PEVK in in Ttn ^?112-158muscles.