Assessment of active state titin's effects on muscle mechanics using finite element modeling

Calcium dependent mechanical behaviors characterize titin's contribution to force production in three-myofilament paradigm: (1) Stiffening of PEVK (Proline, Glutamate, Valine, Lysine) segment, and (2) reduction of free-spring length via N2A-titin binding. This thesis is focused on the introduction of an alternative perspective to the analysis of titin with incorporating epimuscular myofascial loads. Isolated and integrated rat muscle finite element model variations were used with three titin models: passive state titin, active state titin-I and active state titin-II. Results of isolated model showed that active state titin-I and II limits sarcomere shortening (lm = 32.7mm: up to 10% and 20%, respectively). Such shorter sarcomere effect characterizes active state titin's mechanism of effects. Integrated models showed that the shorter sarcomere effect becomes an inconsistent and variable mechanism: Shorter sarcomere effect is further enhanced for proximal fascicle interfaces (by 30.2% and 31.0%, respectively) whereas it is also diminished for remaining fascicles (by 10.3% and 14.0%, respectively), but even a longer sarcomere effect is shown. Overall, titin's mechanism of effect and functionality are manipulated by epimuscular myofascial force transmission. This implies a new approach for the 3-miyofilament model: For the analysis of the components of the contractile machinery, contribution to force production and contribution to muscle mechanics should be assessed with alternative perspectives. Titin's calcium dependent mechanical behaviors belong to former as these increases its stiffness, whereas shorter sarcomere effect belongs to latter as this mechanism further translates its effect to other components as well as to length-force characteristics. These together comprehensively define titin's contribution as a third myofilament.