Background

MyoSim is software that Ken Campbell originally wrote to simulate the mechanical properties of half-sarcomeres. It extends Huxley-based cross-bridge distribution techniques with Ca²⁺ activation and cooperative effects.

This repository contains an implementation of MyoSim written in MATLAB. Other versions of MyoSim have been written in C++ and Python. None of the versions are completely interchangeable. All have strengths and weaknesses.

Theory

MyoSim calculates the force produced by populations of cycling cross-bridges by tracking the number of myosin heads attached to actin with different strains. This approach was originally developed by Andrew Huxley.

The techniques required to simulate cross-bridge distributions using a computer (solving differential equations and interpolation) were described in some of Ken Campbell’s earlier papers.

• A cross-bridge mechanism can explain the thixotropic short-range elastic component of relaxed frog skeletal muscle
• A thixotropic effect in contracting rabbit psoas muscle: prior movement reduces the initial tension response to stretch
• History-dependent mechanical properties of permeabilized rat soleus muscle fibers

The models described in these papers only simulated half-sarcomeres held at a fixed level of activation (i.e. they were not sensitive to the intracellular Ca²⁺ concentration). MyoSim overcame this limitation by coupling cycling cross-bridges to a population of binding sites that were activated by Ca²⁺ and cooperativity. The original paper explained the theory and showed how the software could be used to simulate myosin heads cycling through a variety of different kinetic schemes.

• Dynamic coupling of regulated binding sites and cycling myosin heads in striated muscle

Additional papers building on this technique include:

• Compliance Accelerates Relaxation in Muscle by Allowing Myosin Heads to Move Relative to Actin
• Myocardial relaxation is accelerated by fast stretch, not reduced afterload

MyoSim can also simulate dynamic transitions within the thick filament (OFF to ON states of myosin). The first paper investigating these transitions was:

• Force-Dependent Recruitment from the Myosin Off State Contributes to Length-Dependent Activation

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