Characterization of Cell Membrane Permeability In Vitro Part II: Computational Model of Electroporation-Mediated...

Area of Science:

• Biophysics
• Cell Biology
• Biomedical Engineering

Background:

• Electroporation uses electric fields to create membrane defects for molecular delivery.
• Validating computational models of electroporation with quantitative uptake data is challenging.
• Part I introduced a fluorescence microscopy method for measuring membrane permeability and transport.

Purpose of the Study:

• To develop and validate a two-stage ordinary differential equation model for cellular electroporation.
• To quantitatively assess molecular uptake and cell membrane permeability.
• To investigate the effects of buffer conductivity and multipulse schemes on electroporation.

Main Methods:

• Utilized quantitative molecular uptake data from Part I.
• Developed a two-stage ordinary differential equation model.
• Fitted the model using experimental data across various electric field strengths, pulse durations, and buffer solutions.

Main Results:

• A low-conductivity 4-(2-hydroxyethyl)-1 piperazineethanesulfonic acid buffer accelerated molecular transport compared to other buffers.
• Interpulse delay up to 100 μs did not significantly affect molecular uptake in multipulse schemes.
• Per-pulse permeability enhancement decreased with an increasing number of pulses.

Conclusions:

• This is the first validated ordinary differential equation model for electroporation incorporating quantitative uptake data, membrane permeability, and charging.
• The findings provide insights into optimizing electroporation protocols for enhanced molecular delivery.
• Buffer conductivity and pulse number are critical factors influencing electroporation efficiency.