Cationic peptide exposure enhances pulsed-electric-field-mediated membrane disruption

Area of Science:

• Biophysics
• Cell Biology
• Biotechnology

Background:

• Pulsed electric fields (PEFs) offer a method for irreversible electroporation to destroy cells.
• Reducing PEF intensity via molecular delivery could enhance its applicability.
• Charged molecules on cell surfaces may create localized electric potential enhancements, lowering PEF requirements.

Purpose of the Study:

• To investigate if cationic peptides can enhance PEF-induced plasma membrane disruption.
• To determine if charged molecules can lower the threshold for electroporation.

Main Methods:

• Leukemia cells were exposed to PEFs (1-2 kV/cm) with varying concentrations of polyarginine.
• Propidium iodide (PI) uptake was monitored in real-time to assess membrane integrity.
• Cell PI fluorescence over time was analyzed to quantify membrane disruption.

Main Results:

• Exposure to >50 microg/ml polyarginine resulted in immediate and high PI uptake, indicating severe membrane disruption.
• In the absence of peptide, cells showed minimal membrane disruption at the tested PEF intensities.
• PI entered cells through the anode-facing membrane when exposed to cationic peptide.

Conclusions:

• Cationic peptides reduce the PEF intensity required for rapid and irreversible membrane disruption.
• Peptide exposure enables irreversible membrane disruption at sub-electroporation intensities.
• Cationic peptides, combined with cell targeting, show promise for targeted destruction of unwanted cells.