Electropermeabilization and electrostimulation by picosecond pulses

Abstract

Biological effects of picosecond electric pulses have not been studied as widely as those for longer pulses. The research has been restricted mainly due to the lack of pulse generators and exposure systems. Recent advance in generators capable of producing ultrashort electric pulses has alleviated the restriction and allowed more biological studies in this short-pulse regime. As the picosecond pulse duration is shorter than a plasma membrane charging time constant and a cell's dielectric relaxation time, the distribution of electric field across the cell is determined by the dielectric properties of cell's structures. The plasma membrane in this case has the highest field, similar to the case when it is charged by longer pulses through resistive current. For picosecond pulses, direct plasma membrane poration requires very high electric fields. Cells that have voltage-gated channels however can be permeabilized by single, 500 ps pulse with the electric field of 190 kV/cm. This is evidenced by a lack of Ca2+ response in Chinese hamster ovary (CHO) cells and significant calcium uptake in murine pituitary tumor (GH3) cells and neuroblastoma-glioma hybrid (NG108) cells, which both have rich calcium voltage-gated channels. Because the pulse duration is much shorter than the standard channel opening time, it can be speculated that the permeabilization caused by picosecond pulses is different from standard channel opening, which presents a unique opportunity for a deeper understanding of the biophysics of both voltage-gated channel conduction and electroporation. Nevertheless, the development of approaches to lower the electric field is warranted for practical applications, such as stimulation that employs antennas as noninvasive pulse delivery device.