Microdosimetric study for nanosecond pulsed electric fields on a cell circuit model with nucleus

Area of Science:

• Biophysics
• Computational Biology
• Cellular Electroporation

Background:

• Increasing interest in intense, short electric pulses for biological effects on cell membranes.
• Need for microdosimetric models incorporating intracellular organelles like the nucleus.
• Transmembrane potential (TMP) is critical for understanding electroporation effects.

Purpose of the Study:

• To propose a circuit model of the cell including the nucleus with dielectric dispersion.
• To investigate the impact of nuclear dielectric properties on induced transmembrane potential (TMP).
• To determine the necessity of dispersive nucleus models for short electric pulses.

Main Methods:

• Development of a comprehensive cell circuit model incorporating dielectric dispersion of all compartments.
• Simulation of electric pulse effects on transmembrane potential (TMP) across plasma and nuclear membranes.
• Comparison of model results with and without nuclear dielectric dispersion for various pulse durations.

Main Results:

• Significant differences in TMP were observed for pulses shorter than 10 nanoseconds when including nuclear dielectric dispersion.
• Short pulses (<10 ns) are more effective in intracellular poration, correlating with calculated TMP.
• Dispersive nucleus models are essential for accurately simulating effects of sub-10 ns pulses due to high spectral content (>100 MHz).

Conclusions:

• Accurate modeling of cell response to short electric pulses requires accounting for nuclear dielectric dispersion.
• The proposed circuit model provides a framework for understanding electroporation dynamics at the sub-10 ns timescale.
• Dispersive nucleus models are unavoidable for pulses with significant frequency components above 100 MHz.