Development of Multi-scale Musculo-skeletal Simulator

This paper presents preliminary status of our project for developing a multi-scale simulation of musculoskeletal system for providing a useful tool in the field of musculo-skeletal physiology and related healthcare issues. Here, a mechanically and physiologically detailed model of skeletal muscles, as a key building block of the system, is considered, in which hierarchical structure of skeletal muscles is modeled by multiple one-dimensional muscle fiber models embedded in a three-dimensional finite element continuum-mechanics model. For modeling the excitation-contraction coupling, we combined models at multiple scales including electrophysiology for action potential generation in muscle fibers, Ca2+ dynamics of sarcoplasmic reticulum describing calcium release and uptake, and cross-bridge dynamics that can reproduce stochastic cross-bridge kinetics with a state transition model of the myosin molecules via Monte Carlo simulation. We then validated each of these models for the excitation-contraction coupling by comparing dynamics of the models with physiological data available in literatures on the muscle function.