Millisecond-scale biochemical response to change in strain

Area of Science:

• Muscle physiology
• Biophysics
• Skeletal muscle contraction

Background:

• Muscle contraction relies on myosin cross-bridge cycling along actin filaments, fueled by adenosine triphosphate (ATP) hydrolysis.
• Understanding the kinetics of cross-bridge states, force generation, and biochemical events like inorganic phosphate (Pi) release is crucial for muscle function.

Purpose of the Study:

• To investigate the relationship between myosin cross-bridge states, force production, and Pi release during mechanical stretch in active mammalian skeletal muscle fibers.
• To elucidate the temporal dynamics of biochemical and mechanical responses during muscle fiber stretch.

Main Methods:

• Experiments were conducted on active mammalian skeletal muscle fibers at 20°C, subjected to ramp stretches.
• Measurements focused on force generation and Pi release kinetics.
• A computational cross-bridge model was employed to simulate these processes, incorporating ATP, ADP, and Pi biochemical states and length-dependent transitions.

Main Results:

• Ramp stretches elicited a rapid rise in force.
• The rate of Pi release decreased abruptly upon stretch initiation and remained suppressed.
• Simulations indicated that stretch promotes rapid cross-bridge detachment and reattachment without immediate Pi release or ATP hydrolysis.

Conclusions:

• Biochemical events on the millisecond timescale are coupled with mechanical and structural changes in contracting muscle fibers during stretch.
• The findings suggest a model where stretch influences cross-bridge cycling dynamics, affecting force generation and Pi release kinetics.