Abstract

Muscle contraction results from myosin heads binding to the actin filament to form cross-bridges, with contractile force dependent on the total number of cross-bridges, the force that each cross-bridge produces, and the myosin attachment time (ton). Muscle shortening and lengthening also influences contractile force, though the direct effect of dynamic length changes on cross-bridge kinetics is unclear. Here, we used a spatially explicit, computational model of muscle force generation to examine how cross-bridge characteristics, such as force per cross-bridge and ton, are affected by various rates of shortening and lengthening (0.1-1 muscle lengths (ML) per second). We found that the force per cross-bridge increased by ∼15% when the sarcomere was lengthened at 0.1 ML/s, and by ∼40% when lengthened at 1.0 ML/s. Conversely, force per cross-bridge decreased during shortening, by ∼25% at 0.1 ML/s and by ∼70% at 1.0 ML/s. Concurrent with these measurements, we found that myosin ton decreased by ∼50-70% as the sarcomere was lengthened at 0.1-1 ML/s, potentially due to increased cross-bridge strain or forced detachment. However, myosin ton increased by ∼50% when the sarcomere was shortened at 0.1 ML/s, but decreased by ∼50% when shortened at 1 ML/s. These data suggest that myosin attachment time is sensitive to length-dependent changes in cross-bridge strain, and that the kinetics may be more sensitive to the rate of shortening than the rate of lengthening. While these results are model dependent and rely upon parameter estimation to fit model predictions with empirical data from skinned fibers, these computational models help illustrate complex system behavior underlying dynamic muscle contraction. These simulation results indicate that sarcomere lengthening may increase the strain borne by individual cross-bridges and decrease myosin ton, and conversely, shortening may decrease cross-bridge strain and prolong myosin ton.

Full Text
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