Investigations on Na+, K+-ATPase energy consumption in ion flow of hydrophilic pores by THz unipolar stimulation.

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.

Theoretical investigation on the effect of terahertz wave on Ca2+ transport in the calcium channel.

The question of whether terahertz (THz) waves can interact with ions in channels of nerve cells and cause a further reaction has attracted much attention. To answer this question, we investigate the spontaneous radiation generated by Ca2+ moving in calcium channels and the effect of THz radiation on the transport of Ca2+ by solving the mathematical physical model through Brownian dynamics (BD) simulations. It is obtained that the moving Ca2+ in a calcium channel can generate electromagnetic radiation, the corresponding spectrum of which is concentrated in the THz range. Meanwhile, both the ion number in the channel and the background temperature are proved to have significant effects on the spontaneous emission spectra. The studies also show that external THz radiation can accelerate Ca2+ transport through the ion channel. These results are expected to provide a theoretical basis for the future treatment of THz waves in the neurological field.

The Effect of KcsA Channel on Lipid Bilayer Electroporation Induced by Picosecond Pulse Trains.

Membrane proteins are the major component of plasma membranes, and they play crucial roles in all organisms. To understand the influence of the presence of KcsA channel on cell membrane electroporation induced by picosecond pulse trains (psPT), in this paper, the electroporation of KcsA membrane protein system and bare lipid bilayer system (POPC) with the applied psPT are simulated using molecular dynamics (MD) method. First, we find that the average pore formation time of the KcsA system is longer than the bare system with the applied psPT. In the KcsA system, water protrusions appear more slowly. Then, the system size effects of psPT in the MD simulations are investigated. When the system size decreases, the average pore formation time of small KcsA membrane protein system is shorter than the bare system with the applied psPT. It is found that the psPT makes the protein fluctuation of small system increase greatly; meanwhile the instability of protein disturbs the water and then affects the water protrusion appearance time. Furthermore, it shows that the protein fluctuation of constant electric field is smaller than that of psPT and no field, and protein fluctuation increases with the psPT repetition frequency increasing.

Probing Nanoelectroporation and Resealing of the Cell Membrane by the Entry of Ca2+ and Ba2+ Ions.

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 <1 ms. The threshold for one 300-ns pulse was at 1.5-2 kV/cm, much lower than >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.

Transient proton transfer of base pair hydrogen bonds induced by intense terahertz radiation.

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.

Interpretation of the molecular mechanism of the electroporation induced by symmetrical bipolar picosecond pulse trains.

Picosecond pulse trains (psPTs) are emerging as a new characteristic diagnostic and therapeutic tool in biomedical fields. To specifically determine the stimulus provided to cells, in this article, we use a molecular dynamics (MD) model to show the molecular mechanisms of electroporation induced by symmetrical bipolar psPTs and predict a bipolar cancellation for the studied picosecond pulses. Electric field conditions that do not cause electroporation reveal that the interfacial water molecules continuously flip and redirect as the applied bipolar psPT reverses, and the molecules cannot keep moving in one direction or leave the lipid-water interface. Based on our simulation results, we determine the threshold for electroporation with symmetrical bipolar psPTs. For a fixed electric field intensity, a lower repetition frequency leads to more rapid electroporation. For a fixed repetition frequency, a higher electric field intensity leads to more rapid electroporation. We found that the water dipole relaxation time decreases as the electric field magnitude increases. Additionally, the influences of the symmetrical bipolar psPT intensity and frequency on the pore formation time are presented. Discrete nanoscale pores can form with the applied psPT at terahertz (THz) repetition frequency. When the psPT amplitude increases or the frequency decreases, the number of water bridges will increase. Moreover, for the first time, the molecular mechanism of bipolar cancellation for the studied picosecond pulse is discussed preliminarily. Our results indicate that the influence of the unipolar picosecond pulse on the interfacial water dipoles will accumulate in one direction, but the bipolar picosecond pulse does not cause this effect.

Terahertz Electric Field-Induced Membrane Electroporation by Molecular Dynamics Simulations.

In this paper, the membrane electroporation induced by the terahertz electric field is simulated by means of the molecular dynamics method. The influences of the waveform and frequency of the applied terahertz electric field on the electroporation and the unique features of the process of the electroporation with the applied terahertz electric field are given. It shows that whether the electroporation can happen depends on the waveform of the applied terahertz electric field when the magnitude is not large enough. No pore appears if the terahertz electric field direction periodically reverses, and dipole moments of the interfacial water and the bulk water keep reversing. The nm-scale single pore forms with the applied terahertz trapezoidal electric field. It is found that the average pore formation time is strongly influenced by the terahertz electric field frequency. An abnormal variation region that shows decline exists on the correlation curve of the average pore formation time and the trapezoidal electric field frequency, whereas the overall trend of the curve is increasing. The decrease of the water oriented polarization degree results in the increase of the electroporation time, and the abnormal variation region appearance may be related to the drastic change of average water hydrogen bond number that is resulted from the resonance of water hydrogen bond network and the applied electric field. Compared to the nanosecond electric pulse and constant electric field, the numbers of the water protrusions and the water bridges are smaller and the pore formation time is relatively longer with the applied terahertz electric field.