A three-state mathematical model of hyperthermic cell death

Area of Science:

• Biophysics
• Cell Biology
• Thermal Medicine

Background:

• Thermal treatments for tissue ablation induce cell death by exceeding critical temperature thresholds.
• Existing cell death models often simplify the process into 'alive' or 'dead' states.

Purpose of the Study:

• To propose and validate a novel three-state model for cell death incorporating a 'vulnerable' intermediate state.
• To investigate the temperature dependence of cell death rate coefficients.
• To extend the model to account for slow cell death dynamics post-heating.

Main Methods:

• Development of a three-state cell death model with temperature-dependent rate coefficients.
• Fitting the model to experimental data from heated co-cultures of hepatocytes and lung fibroblasts.
• Analysis of cell viability at 24 and 48 hours post-heating to refine the model for slow cell death.

Main Results:

• The proposed three-state model demonstrated a very small Root Mean Square (RMS) error when fitted to experimental data.
• Model parameters for fast cell death showed a linear correlation with the percentage of lung fibroblasts in co-cultures.
• No significant co-culture composition dependence was found for slow cell death parameters.

Conclusions:

• The novel three-state model provides a more accurate representation of cell death following thermal treatments.
• A critical post-heating cell viability threshold was identified, predicting progression to cell death.
• The findings have practical implications for improving the accuracy of cell death prediction in thermal ablation therapies.