Intracellular electroporation site distributions: modeling examples for nsPEF and IRE pulse waveforms

Area of Science:

• Biophysics
• Cell Biology
• Medical Engineering

Background:

• Electroporation (EP) utilizes electric fields to permeabilize cell membranes.
• Two main classes of electric field pulses exist: nanosecond pulsed electric fields (nsPEF) and irreversible electroporation (IRE).
• Traditional EP studies often focus on plasma membrane pores and molecular delivery, overlooking intracellular effects.

Purpose of the Study:

• To model and illustrate the expected electroporation responses to nsPEF and IRE using in vitro and in vivo cell systems.
• To investigate the complex electrical behavior and pore dynamics induced by different electric field pulse classes.
• To explore the occurrence and spatial distribution of intracellular electroporation.

Main Methods:

• Employing systems models for single cells (in vitro) and multiple cells (in vivo).
• Simulating responses to two distinct electric field pulse classes: nsPEF (short, high-magnitude) and IRE (longer, lower-magnitude).
• Analyzing passive model responses for small pulses and transient pore populations for larger pulses.

Main Results:

• Models demonstrate that nsPEF and IRE induce non-thermal cell killing without external agents.
• Transient aqueous pore formation significantly increases membrane conductance and alters local electric fields.
• Both nsPEF and IRE were predicted to cause intracellular electroporation, with distinct spatial distributions.

Conclusions:

• Systems models provide insights into complex electroporation dynamics not typically observed in endpoint-focused experiments.
• The study highlights the potential for intracellular electroporation with both nsPEF and IRE.
• Understanding these detailed electrical behaviors and pore distributions is crucial for advancing EP applications.