A cross-bridge cycle with two tension-generating steps simulates skeletal muscle mechanics

Area of Science:

• Muscle physiology
• Biophysics
• Skeletal muscle mechanics

Background:

• Understanding muscle contraction requires accurate models of the cross-bridge cycle.
• Previous models have simplified the tension-generating steps within the cross-bridge cycle.

Purpose of the Study:

• To evaluate if one or two tension-generating steps in cross-bridge cycle models can explain frog skeletal muscle mechanics.
• To determine the contribution of different cross-bridge states to force generation.

Main Methods:

• Developed and refined cross-bridge cycle models using transition-state theory and non-Hookean filament stiffness.
• Utilized simulated annealing and downhill simplex methods for model optimization against experimental data.
• Analyzed model performance in explaining force-velocity relationships and tension responses to length changes.

Main Results:

• Models with a single tension-generating step were inadequate, showing low efficiency and poor data fit.
• The best two-step model (stroke distances 5.6 and 4.6 nm) accurately predicted experimental data.
• This two-step model achieved up to 38% efficiency during shortening and detailed the distribution of cross-bridge states under isometric and dynamic conditions.

Conclusions:

• A two-step cross-bridge cycle model is essential for accurately describing skeletal muscle force-velocity and length-tension relationships.
• The distribution of cross-bridge states varies significantly between isometric, shortening, and lengthening contractions.
• The model provides insights into the mechanical states of myosin heads during different phases of muscle activity.