Ultrastructural changes in hepatocellular carcinoma cells induced by exponential pulses of nanosecond duration delivered via a transmission line.

ABSTRACT

Clinical applications of high-intensity pulsed electric fields have proven useful in ablating solid tumors. However, novel ideas for the development of an effective tumor ablation device are urgently needed. Here, we studied cellular effects of the nanosecond exponential pulse, which is generated by a capacitor-discharging circuit and delivered via a transmission line. Pulses of peak voltage boosted by transmission line oscillation possess high capability to induce swelling and to cause loss of viability in cells. The appropriate parameter of the pulse was selected to investigate the ultrastructural changes in swollen cells, which present smoothened plasma membrane, loss of microvilli, and lowered cytoplasm electron density. We propose the equivalent force field hypothesis to understand the mechanism underlying cell swelling induced by pulsing. Wrinkles on the plasma membrane might indicate recovery from cell swelling, and this was verified by co-culture of pulsed PKH26-Cells with sham-treated PKH67-Cells. We concluded that the ultrastructural changes, such as irregular pores formed on the plasma membrane, were mainly induced by the effect of electric pulse applied on the charged molecules in the membrane.