Calcium Diffusion Simulation in a 3D Sarcomere Model

Computational modeling of the muscle activation process

Graduate students worked with a spatially realistic 3D model of a half-sarcomere to simulate calcium diffusion, buffering, and reuptake during activation and fatigue. The model supports broader understanding of excitation–contraction coupling under different loading conditions.

Computational Approach

Our model uses a stochastic agent-based approach to simulate:

  • Calcium ion release from the sarcoplasmic reticulum
  • Diffusion through the sarcomeric space
  • Binding to troponin C and other calcium buffers
  • Reuptake by SERCA pumps

Technical Implementation

The simulation is built using MCell, a Monte Carlo simulator for cellular microphysiology, and analysed with custom Python scripts. The 3D geometry of the sarcomere is reconstructed from electron microscopy data.

Research Impact

This computational model helps bridge the gap between molecular mechanisms and whole-muscle function, offering insights into how structural changes affect calcium handling during muscle activation and fatigue. The findings have implications for understanding muscle disorders and developing targeted interventions.

Publication

The methods and findings of this research were published in PLOS Computational Biology:

Holash RJ, MacIntosh BR (2019) A stochastic simulation of skeletal muscle calcium transients in a structurally realistic sarcomere model using MCell. PLOS Computational Biology 15(3): e1006712.