Obstructed metabolite diffusion within skeletal muscle cells in silico

Area of Science:

• Biophysics
• Cellular Biology
• Computational Biology

Background:

• Skeletal muscle cells contain complex intracellular structures that influence metabolite diffusion.
• Understanding diffusion is crucial for cellular metabolism and function.
• Previous models suggested intracellular structures limit diffusion, but lacked detailed simulation.

Purpose of the Study:

• To model 3D diffusion of low molecular weight metabolites within a skeletal muscle cell.
• To investigate the impact of intracellular structures, termed 'macrocompartments', on diffusion coefficients.
• To compare simulation results with experimental data on phosphocreatine diffusion.

Main Methods:

• Employed Monte Carlo simulation technique to model particle movement in 3D.
• Incorporated structural elements: actin-myosin filaments, sarcoplasmic reticulum, mitochondria, and macrocompartments.
• Calculated apparent diffusion coefficients in radial (D(app)(⊥)) and axial (D(app)(II)) directions.

Main Results:

• Axial diffusion (D(app)(II)) was modeled as unrestricted.
• Radial diffusion (D(app)(⊥)) decreased over time due to collisions with obstacles.
• Simulations accurately reproduced experimental NMR data for phosphocreatine diffusion in goldfish muscle.

Conclusions:

• Reflections from low-permeable macrocompartment borders are essential for matching experimental diffusion data.
• Hypothetical macrocompartments, with ~99.8% coverage, significantly contribute to time-dependent radial diffusion restriction.
• The model provides a framework for understanding diffusion limitations in complex cellular environments.