Nanoelectropulse-induced phosphatidylserine translocation

P. Thomas Vernier, Yinghua Sun, Laura Marcu, Cheryl M. Craft, Martin A. Gundersen

Research output: Contribution to journalArticle

154 Scopus citations

Abstract

Nanosecond, megavolt-per-meter, pulsed electric fields induce phosphatidylserine (PS) externalization, intracellular calcium redistribution, and apoptosis in Jurkat T-lymphoblasts, without causing immediately apparent physical damage to the cells. Intracellular calcium mobilization occurs within milliseconds of pulse exposure, and membrane phospholipid translocation is observed within minutes. Pulsed cells maintain cytoplasmic membrane integrity, blocking propidium iodide and Trypan blue. Indicators of apoptosis-caspase activation and loss of mitochondrial membrane potential-appear in nanoelectropulsed cells at later times. Although a theoretical framework has been established, specific mechanisms through which external nanosecond pulsed electric fields trigger intracellular responses in actively growing cells have not yet been experimentally characterized. This report focuses on the membrane phospholipid rearrangement that appears after ultrashort pulse exposure. We present evidence that the minimum field strength required for PS externalization in actively metabolizing Jurkat cells with 7-ns pulses produces transmembrane potentials associated with increased membrane conductance when pulse widths are microseconds rather than nanoseconds. We also show that nanoelectropulse trains delivered at repetition rates from 2 to 2000 Hz have similar effects, that nanoelectropulse-induced PS externalization does not require calcium in the external medium, and that the pulse regimens used in these experiments do not cause significant intra- or extracellular Joule heating.

Original languageEnglish (US)
Pages (from-to)4040-4048
Number of pages9
JournalBiophysical Journal
Volume86
Issue number6
DOIs
StatePublished - Jun 2004

ASJC Scopus subject areas

  • Biophysics

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    Vernier, P. T., Sun, Y., Marcu, L., Craft, C. M., & Gundersen, M. A. (2004). Nanoelectropulse-induced phosphatidylserine translocation. Biophysical Journal, 86(6), 4040-4048. https://doi.org/10.1529/biophysj.103.037945