Cellular apoptosis by nanosecond, high-intensity electric pulses: Model evaluation of the pulsing threshold and extrinsic pathway

Jiahui Song, Ravindra P. Joshi, Stephen J. Beebe

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

A simple, bistable rate-equation based model is used to predict trends of cellular apoptosis following electric pulsing. The caspase-8 extrinsic pathway with inherent delays in its activation, cytochrome c release, and an internal feedback mechanism between caspase-3 and cleavage of Bid are incorporated. Results obtained were roughly in keeping with the experimental cell-survival data and include an electrical pulse-number threshold followed by a near-exponential fall-off. The extrinsic caspase-8 mechanism is predicted to be more sensitive than the mitochondrial intrinsic pathway for electric pulse induced cell apoptosis. Also, delays of about an hour are predicted for detectable molecular concentration increases following electrical pulsing. Finally, our results suggest that multi-needle electrode systems with adjustable field orientations would likely enhance apoptosis in the context of pulsed voltage-induced inactivation of tumor cells.

Original languageEnglish
Pages (from-to)179-186
Number of pages8
JournalBioelectrochemistry
Volume79
Issue number2
DOIs
StatePublished - Oct 2010

Keywords

  • Apoptosis
  • Cell survival
  • Electrical pulsing
  • Mechanisms
  • Numerical model

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