Excitation and electroporation by MHz bursts of nanosecond stimuli

Andrei G. Pakhomov, Shu Xiao, Vitalij Novickij, Maura Casciola, Iurii Semenov, Uma Mangalanathan, Vitalii Kim, Christian Zemlin, Esin Sozer, Claudia Muratori, Olga N. Pakhomova

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Intense nanosecond pulsed electric field (nsPEF) is a novel modality for cell activation and nanoelectroporation. Applications of nsPEF in research and therapy are hindered by a high electric field requirement, typically from 1 to over 50 kV/cm to elicit any bioeffects. We show how this requirement can be overcome by engaging temporal summation when pulses are compressed into high-rate bursts (up to several MHz). This approach was tested for excitation of ventricular cardiomyocytes and peripheral nerve fibers; for membrane electroporation of cardiomyocytes, CHO, and HEK cells; and for killing EL-4 cells. MHz compression of nsPEF bursts (100–1000 pulses) enables excitation at only 0.01–0.15 kV/cm and electroporation already at 0.4–0.6 kV/cm. Clear separation of excitation and electroporation thresholds allows for multiple excitation cycles without membrane disruption. The efficiency of nsPEF bursts increases with the duty cycle (by increasing either pulse duration or repetition rate) and with increasing the total time “on” (by increasing either pulse duration or number). For some endpoints, the efficiency of nsPEF bursts matches a single “long” pulse whose amplitude and duration equal the time-average amplitude and duration of the bursts. For other endpoints this rule is not valid, presumably because of nsPEF-specific bioeffects and/or possible modification of targets already during the burst. MHz compression of nsPEF bursts is a universal and efficient way to lower excitation thresholds and facilitate electroporation.

Original languageEnglish
Pages (from-to)759-764
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume518
Issue number4
DOIs
StatePublished - Oct 22 2019

Keywords

  • Electropermeabilization
  • Electroporation
  • Electrostimulation
  • Nanosecond pulses
  • Temporal summation

Fingerprint

Dive into the research topics of 'Excitation and electroporation by MHz bursts of nanosecond stimuli'. Together they form a unique fingerprint.

Cite this