Picosecond and Terahertz Perturbation of Interfacial Water and Electropermeabilization of Biological Membranes

Abstract

Nonthermal probing and stimulation with subnanosecond electric pulses and terahertz electromagnetic radiation may lead to new, minimally invasive diagnostic and therapeutic procedures and to methods for remote monitoring and analysis of biological systems, including plants, animals, and humans. To effectively engineer these still-emerging tools, we need an understanding of the biophysical mechanisms underlying the responses that have been reported to these novel stimuli. We show here that subnanosecond (≤ 500 ps) electric pulses induce action potentials in neurons and cause calcium transients in neuroblastoma-glioma hybrid cells, and we report complementary molecular dynamics simulations of phospholipid bilayers in electric fields in which membrane permeabilization occurs in less than 1 ns. Water dipoles in the interior of these model membranes respond in less than 1 ps to permeabilizing electric potentials by aligning in the direction of the field, and they re-orient at terahertz frequencies to field reversals. The mechanism for subnanosecond lipid electropore formation is similar to that observed on longer time scales — energy-minimizing intrusions of interfacial water into the membrane interior and subsequent reorganization of the bilayer into hydrophilic, conductive structures.

Electroporation by subnanosecond pulses

“…The present work was aimed at further exploring psEP-induced electroporation by electrophysiological and optical membrane potential detection techniques. Bioeffects of psEP remain essentially an uncharted territory, with current knowledge limited to a few isolated reports [17] , [24] , [25] , [26] . Below we demonstrate that even a single psEP at 190 kV/cm can permeabilize cell membrane, and that psEP- and nsEP-porated membranes share similar features.…”

Irreversible electroporation for the treatment of cardiac arrhythmias

“…[23] Reported pictures of large pores obtained by freeze-fracture electron microscopy [25] are attributed to artifacts of the technique [23]. Nevertheless, it must be noted that recent studies based on molecular dynamic simulations indicate that, after establishing the required TMV, aqueous pores are created in the lipid bilayer in a few nanoseconds [26] or less [27], provide convincing evidence that pores are the most probable mechanism of the initial membrane perturbation.…”

Numerical Study of Voltage-Gated Ca2+ Transport Irradiated by Terahertz Electromagnetic Wave

“…Thus, joule loss can be ignored and the electrical power in (18) only results from electric polarization loss. In this case, by neglecting joule loss and rearranging (17), (18) and (19), the temperature variation with time in part p of the system is,…”

“…Furthermore, it is known that the electric pulse containing the low frequency region, for example, unipolar or bipolar nanosecond electric pulse, opens pathways in the plasma membrane for the entry of extracellular Ca 2+ ions [18]- [20]. Additionally, molecular dynamics simulations show that the electropore formation for the entry of extracellular Ca 2+ ions by the applied picosecond pulse is similar to that by nanosecond electric pulse [17]. Therefore, it is uncertain to attribute the entry of Ca 2+ ions to terahertz component, low frequency component or both.…”

“…The non-thermal increase in intracellular Ca 2+ concentration in neuroblastoma cells is observed, and the phospholipid bilayer membrane electroporation for ion transport is simulated with molecular dynamics simulations under the radiation of picosecond electric pulse, whose fast rise edge contains signal component in terahertz frequency [17]. Although the applied picosecond electric pulse [17] contains a few amounts of energy in terahertz spectral region, the pulse is a broadband signal which also contains much more energy in low frequency region from megahertz to kilohertz frequency, including direct current. Furthermore, it is known that the electric pulse containing the low frequency region, for example, unipolar or bipolar nanosecond electric pulse, opens pathways in the plasma membrane for the entry of extracellular Ca 2+ ions [18]- [20].…”