Intracellular electroporation site distributions: Modeling examples
for nsPEF and IRE pulse waveforms
T. R. Gowrishankar, A. T. Esser, K. C. Smith, R. S. Son, and J. C. Weaver Conf. Proc. IEEE Eng. Med. Biol. Soc. 2011. 732-5. 2011.
We illustrate expected electroporation (EP) responses to two classes of
large electric field pulses by employing systems models, one of a cell
in vitro and the other of multiple cells in vivo.
The first pulse class involves "nsPEF" (nanosecond pulsed electric fields).
The durations are less than a microsecond, but the magnitudes are extremely
large, often 10 kV/cm or more,
and all of the pores remain small.
The second class involves "IRE" (irreversible electroporation).
Durations are many microseconds to several milliseconds, but with
magnitudes smaller than 10 kV/cm,
and a wide range of pore sizes evolves.
A key feature of both pulse classes is non-thermal cell killing
by multiple pulses without delivering external drugs or genes.
For small pulses the models respond passively
(no pore creation) providing negative controls.
For larger pulses transient aqueous pore populations evolve.
These greatly increase local membrane conductance temporarily, causing rapid
redistribution of fields near and within cells.
This complex electrical behavior is generally not revealed by
experiments reporting biological end points
resulting from cumulative ionic and molecular transport through
The underlying, heterogeneous pore population distributions are also
not obtained from typical experiments.
Further, traditional EP applications involving molecular delivery
are usually assumed to create pores solely in the outer, plasma membrane (PM).
In contrast, our examples support the occurrence of intracellular EP
by both nsPEF and IRE, but with different intracellular spatial
distributions of EP sites.