Multi-scale modeling and simulation of skeletal muscles with different fatigue degrees based on microphysiology.

The ability for skeletal muscle to constantly generate force is limited by the muscle fatigue. The calcium ion plays a significant role of the cross-bridge cycle under fatigue conditions in the force generation of skeletal muscle. To uncover complicated fatigue behavior, we conducted a multi-scale model of skeletal muscle based on cellular biochemical events. We also parameterized our model to obtain the characteristics of the change of concentration of phosphate ions and phosphate compounds in the myoplasm. The results provided evidence that under different fatigue levels, the peak of muscle strength decreases with the increase of muscle fatigue, which proves that the synergistic effect of muscle filaments and phosphate will affect the circulation of calcium ions, thereby affecting muscle fatigue and generation of muscle force. We used our modeling approach to bring new insights into the effect of phosphate ions and synergistic effect of myofilaments.