Nanoelectropulse Intracellular Perturbation and Electropermeabilization Technology: Phospholipid Translocation, Calcium Bursts, Chromatin Rearrangement, Cardiomyocyte Activation, and Tumor Cell Sensitivity

Abstract

Nanosecond, megavolt-per-meter pulsed electric fields scramble the asymmetric arrangement of phospholipids in the plasma membrane, release intracellular calcium, trigger cardiomyocyte activity, and induce apoptosis in mammalian cancer cells, without the permeabilizing effects associated with longer, lower-field pulses. Dose dependencies with respect to pulse width, amplitude, and repetition rate, and total pulse count are observed for all of these phenomena. Sensitivities vary among cell types; cells of lymphoid origin growing in suspension are more susceptible to nanoelectropulse exposure than solid tumor lines. Simple electrical models of the cell are useful for first-order explanations, but more sophisticated treatments will be required for analysis and prediction at both biomolecular and tissue levels.

High-Order Quadratures for the Solution of Scattering Problems in Two Dimensions

“…A single nanosecond pulse causes depolarization, calcium waves, and contraction of cardiomyocyte fibers [6]. Adrenal chromaffin cells also respond to a single pulse as short as 3 ns with elevated intracellular calcium levels and catecholamine release.…”

“…Nanosecond, megavolt-per-meter pulsed electric fields nondestructively perturb the intracellular environment, causing calcium bursts [1,2], eosinophil sparklers [3], vacuole permeabilization [4], nuclear chromatin rearrangement [5], activation of excitable cells (cardiac myocytes and adrenal chromaffin cells) [6], and the appearance of apoptotic indicators such as release of cytochrome c into the cytoplasm [7], loss of mitochondrial membrane potential, and caspase activation [8,9]. Nanoelectropulse-induced killing of cancer cells and shrinking of tumors has been demonstrated in vitro and in vivo [10,11].…”

Compact high voltage subnanosecond pulsed power delivery system for biological applications

“…Experiments have shown that nanoelectropulses (ns MV/m electric fields) induce apoptosis in malignant cells without damaging the external cell membrane [1][2][3]. Molecular dynamics simulations indicate that subnanosecond 5-20 MV/m pulses could minimize nanoporation of the cell membrane, and allow intracellular electro-manipulation to dominate over membrane effects [2].…”

Compact Subnanosecond Pulse Generator Using Avalanche Transistors for Cell Electroperturbation Studies

“…[1][2][3] These effects have, among other things, generated interest in the electromanipulation of intracellular structures for inducing apoptosis and understanding gene transfection mechanisms.…”