Meeting Abstract
In striated muscle, the giant protein titin spans the entire length of a half-sarcomere and extends from the backbone of the thick filament, reversibly attaches to the thin filaments, and anchors to the dense protein network of the z-disk capping the end of the half-sarcomere. However, little is known about the relationship between the basic mechanical properties of titin and muscle contractility. Here, we build upon our previous multi-filament, spatiotemporal computational model of the half-sarcomere by incorporating the nonlinear mechanics of titin filaments in the I-band. We vary parameters of the nonlinearity to understand the effects of titin stiffness on contraction dynamics and efficiency. We do so by simulating isometric contraction for a range of sarcomere lengths (SL; 1.5–3.0 μm). Intermediate values of titin stiffness accurately reproduce the passive force–SL relation for skeletal muscle. The maximum force–SL relation is not affected by titin for SL < 2.75 μm. However, for SL > 3.0 μm, maximum force significantly increases from 101 ± 2 pN to 112 ± 3 pN as titin stiffness increases. Additionally, by monitoring ATP consumption, we measure contraction efficiency as a function of titin stiffness. We find that at SL = 3.0 μm, efficiency significantly increases from 13.5 ± 0.4 pN/ATP to 15.5 ± 0.6 pN/ATP when increasing titin stiffness, with little or no effect below 3.0 μm. Taken together, our results point to a unique role of titin in determining muscle contractile efficiency.
