The principal bioeffect of the nanosecond pulsed electric field (nsPEF) is a lasting cell membrane permeabilization, which is often attributed to the formation of nanometer-sized pores. Such pores may be too small for detection by the uptake of fluorescent dyes. We tested if Ca²⁺, Cd²⁺, Zn²⁺, and Ba²⁺ ions can be used as nanoporation markers. Time-lapse imaging was performed in CHO, BPAE, and HEK cells loaded with Fluo-4, Calbryte, or Fluo-8 dyes. Ca²⁺ and Ba²⁺ did not change fluorescence in intact cells, whereas their entry after nsPEF increased fluorescence within 7 kV/cm for the formation of larger pores that admitted YO-PRO-1, TO-PRO-3, or propidium dye into the cells. Ba²⁺ entry caused a gradual emission rise, which reached a stable level in 2 min or, with more intense nsPEF, kept rising steadily for at least 30 min. Ca²⁺ entry could elicit calcium-induced calcium release (CICR) followed by Ca²⁺ removal from the cytosol, which markedly affected the time course, polarity, amplitude, and the dose-dependence of fluorescence change. Both Ca²⁺ and Ba²⁺ proved as sensitive nanoporation markers, with Ba²⁺ being more reliable for monitoring membrane damage and resealing.

This paper simulates Ca2+ transmembrane transport through voltage-gated Ca2+ channels in response to terahertz electromagnetic irradiation. The active transport of Ca2+ ions is taken into considerations in the Ca2+ transport. Temperature variations due to terahertz electromagnetic loss in physiological medium are simulated. The electromagnetic interaction between terahertz fields and physiological mobile ions at the cellular level is deduced from relativistic electrodynamics. It shows that effects of 0.1 ~ 3 THz electromagnetic fields on cell mobile ions are primarily due to effects of electric fields, and effects of magnetic fields at the cellular level are insignificant. In addition, numerical simulation reveals that terahertz irradiation causes vibration of membrane potential, which is able to activate voltage-gated Ca2+ channels. Besides, bioeffects of terahertz frequency, irradiation duration and electric intensity on the increment of intracellular Ca2+ concentration due to activation of voltage-gated Ca2+ channels are revealed. Meanwhile, numerical results show that temperature rises are inconsequential in the case of different irradiation parameters, indicating the non-thermal bioeffects of voltage-gated Ca2+ transmembrane transport due to terahertz irradiation. Furthermore, the results also reveal that thermal bioeffect can be significant if the irradiation duration is raised long enough for high-dose terahertz irradiation. The numerical simulations lay the basis for understanding the bioeffects of terahertz irradiation on Ca2+ transmembrane transport and pave the way for further exploration in modulation of intracellular Ca2+ concentration with terahertz electromagnetic wave.

Local oriented intense electric fields play a vital role in biochemical reactions such as enzyme catalysis. Many researchers have gradually applied external oriented electric fields to control specific chemical reactions. The rapidly developing intense field of terahertz technology can provide a strong enough oriented electric field with specific polarization direction on a sub-picosecond timescale, which matches the timescale and intensity requirements for affecting specific ultrafast chemical reactions. Inspired by this, this paper theoretically studied the full quantum model of the proton transfer process in DNA base pair hydrogen bonds induced by intense terahertz radiation (ITR) with a sub-picosecond-oriented electric field through simulation based on density functional theory (DFT) and the Schrodinger equation. The result shows that the ITR with an electric field intensity up to 10 GV m⁻¹ in a specific polarization direction can precisely control the proton transfer process in the base pair hydrogen bonds. Based on flexible optical methods, the ITR is expected to go beyond the traditional techniques for applying strong electric fields to chemical systems through solid electrodes and become a catalyst for controlling chemical reactions or a scalpel to manipulate molecular structures.

The voltage-gated calcium influxes modulated with terahertz Gaussian pulse is presented in this paper, and temperature rise is evaluated to monitor the terahertz thermal effects involved in the modulation. From the numerical results, inhibition effect on voltage-gated calcium influx because of the loss of the influx from electric drift is transparently revealed in the modulation with terahertz Gaussian pulse. And the inhibition effect becomes significant reflected by considerable reduction in voltage-gated calcium influx as the irradiated amplitude is raised intense enough. Compared to the terahertz sinusoidal wave, Gaussian pulse reduces the inhibition effect dramatically. The decrease in the increment of intracellular calcium concentration with the irradiated amplitude due to the inhibition effect is substantially relieved by the modulation of the calcium influx with terahertz Gaussian pulse. The thermal analyses reveal that the modulation is non-thermal effect. Meanwhile, to raise the intracellular calcium concentration to a same amount by means of the voltage-gated calcium influx, application of terahertz Gaussian pulse induces much less concurrent temperature rise than application of terahertz sinusoidal wave of the same amplitude that is intense enough to cause the inhibition effect. Additionally, terahertz Gaussian pulse irradiation remains the dependence of the increment of the calcium concentration on the irradiated time duration and frequency in terahertz sinusoidal wave irradiation. These numerical results lay the theoretical basis for the modulation of voltage-gated calcium fluxes with terahertz Gaussian pulse and for further potential clinical applications of terahertz Gaussian pulse.

Irradiation of terahertz electromagnetic wave including its short-wave band in infrared wave shows broad and important application prospects in biological science due to its noninvasive and nonionizing nature. Cell membrane is an important biological barrier for keeping cell integrity and homeostasis, and it is also the cellular structure that electromagnetic fields act first on in the case of terahertz irradiation. The responses of cell membrane to the electromagnetic fields are the mechanisms for most of the biological effects of terahertz irradiation. First, in this paper are expatiated the application safety of terahertz irradiation and its new application prospects in life medicine, neural regulation and artificial intelligence. Then, systematically described are the researches and developments in the biological effects of cell membrane under terahertz electromagnetic irradiation from the following four aspects: the dielectric response characteristics of phospholipid membrane to terahertz electromagnetic irradiation, the transmembrane transport of ions through membrane ion channel proteins under the irradiation, the transmembrane transport of macromolecules and ions through phospholipid membrane under the irradiation, and the potential applications and role of biological effects of cell membrane under the irradiation. Meanwhile, introduced in this paper are the scientific discoveries that terahertz electromagnetic irradiation is able to activate voltage-gated calcium channels, voltage-gated potassium channels and active transport calcium channels in cell membrane and to create hydrophilic pores on the phospholipid membrane of cell membrane. Finally, the directions of future efforts to study the biological effects of cell membrane under terahertz irradiation are presented.

Terahertz science and technology has recently shown new application prospects in artificial intelligence. It is found that terahertz unipolar stimulation can activate cell membrane hydrophilic pores. However, the behaviors of Na+, K+-ATPase and energy consumption during this period remain unknown. This paper investigates these behaviors by Na+, K+-ATPase and electroporation models, based on the interaction theory between terahertz fields and ions at the cellular level. The effective diameters of life ions are considered in the aqueous solution. From results, Na+, K+-ATPases can be activated and stay for a while before close after the stimulation. Their life ion flows are far lower than the flows via the pores. And their power dissipation is as low as 10⁻¹¹ W in both rat neostriatal neurons and guinea pig ventricular myocytes. The results keep tenable in 0.1–1.2 THz. These lay the basis for investigations of information communication mechanisms in cells under terahertz stimulation.