Theoretical And Experimental Study On Inorganic Ion Transmembrane Transport For Biological Cell Under Electromagnetic Radiation

To realize the applications of electromagnetic radiation in life science and biomedicine,such as therapies of heart disease,neurodegenerative disease,tumor ablation,microorganism deactivation,and so on,non-thermal biological effects of recently emerged electromagnetic radiation are becoming active research fields nowadays.In this dissertation,research topic is the transport of inorganic ions through cell membrane in response to the electromagnetic radiation.The key research contents focus on the biophysical process of calcium transmembrane transport through physiological channels radiated by nanosecond pulsed electric fields(ns PEFs)and terahertz(THz)electromagnetic fields,and the experimental method for the detection of cell membrane nanopores with barium transmembrane transport.The primary research work and innovations are as follows.1.The model of transport flux of calcium ions through cell membrane physiological channels is proposed.And the algorithms for the numerical simulations of the transmembrane transport of calcium ions through voltage-gated channels,active transport channels in the cell membrane and the changes of intracellular calcium concentration caused by the transmembrane transport calcium flux in response to ns PEF are provided.Based on that,the calcium transport through cell membrane physiological channels in response to ns PEF is numerically simulated.The validity of the theoretical model is indicated by comparing the numerical results with the experimental observations reported.And the nonlinear regulating effects of the pulse width and electric field amplitude in ns PEF on the transport of calcium flux through the physiological channels and the corresponding changes in intracellular calcium concentration are concluded.2.Based on the relativistic electromagnetism,the theory of the electromagnetic interaction between THz fields and physiological ions at the cellular level and at the ion-channel level is proposed.By the combination of the interaction theory and thermodynamic principles,the numerical calculation method of the absorption loss of THz electromagnetic radiation in cell physiological environment is provided.Then,by utilizing the electromagnetic interaction theory between THz fields and physiological ions at the cellular level,with the combination of the above proposed model of the transport flux of calcium ions through cell membrane physiological channels,taking THz sinusoidal wave as an example,calcium transmembrane transport through voltage-gated calcium channels(VGCCs)under THz electromagnetic radiation is numerically simulated.The numerical results show that THz electromagnetic radiation is able to open the VGCCs.The validity of this numerical conclusion is indicated by comparing with a series of voltage-gated ion channel models reported at the molecular scale.And the regulating effects of the electromagnetic parameters in the THz sinusoidal wave on the voltage-gated calcium flux and the system temperature variations are given.Besides,by utilizing the above established codes for numerical simulation on calcium transmembrane transport through VGCCs in response to THz electromagnetic radiation,THz Gaussian pulse radiation is proposed for the advanced modulation of the voltage-gated calcium flux and depressed thermal effects compared to the THz sinusoidal wave radiation.3.The model of ionic solution at the molecular scale is set up,and the numerical method for the calculation of the electric field due to ions in the traditional Brownian dynamics simulation of thermal motion of ions in the solution is revised by utilizing the theory on nonlinear response of aqueous solvent to microscopic electric fields at the molecular scale.The corresponding algorithms for the numerical simulation are given.Based on that,the dynamic equilibrium states of ionic solutions are numerically simulated.The rationality of the theoretical model revision is indicated by comparing with the numerical simulation result of the dynamic equilibrium state without the revision.Meanwhile,numerical results show that the profile of dielectric constant of aqueous solvent at the molecular scale in ionic solution is spatially non-uniform.Then,the dielectric constant profiles of aqueous solvent at the molecular scale in the presence of ns PEF are numerically simulated.The numerical results reveal that ns PEF is capable of significantly lowering the dielectric constant of aqueous solvent at the molecular scale as long as the electric field amplitude is high enough.4.On the basis of the above proposed electromagnetic interaction theory between THz fields and physiological ions at the ion-channel level,the physical model of ion channel in the presence of THz electromagnetic radiation is set up.The dielectric response of aqueous solution in the ion channel to THz electromagnetic radiation is derived by calculating the polarization charge at the interface between channel protein and aqueous solution based on the interface condition of the electric field from the Maxwell equations.Then,the dynamic process of ion motion and transmembrane transport along the axial line in the channel in the presence of THz electromagnetic radiation is numerically simulated with Brownian dynamics simulation method.The numerical results reveal the biophysical process that THz electromagnetic radiation is able to drive physiological ions across the energy barrier in the channel and causes the transmembrane transport of the ions.5.With the help of the experimental technology of the fluorescent labeling and measurement of ions,the experimental feasibilities of the detection of cell membrane nanopores with three kinds of non-physiological bivalent cations: cadmium,zinc or barium ions are analyzed by testing the fluorescence stability of biological cell whose cell membrane lacks VGCCs in response to extracellular stimulation of cadmium,zinc or barium ions.Then,the new experimental method for the detection of cell membrane nanopores with barium transmembrane transport in response to ns PEF is proposed.And the comparisons among the proposed method and the experimental methods with calcium ions and YO-PRO-1 dye molecules for the nanopore detection are provided.The theoretical and experimental results lay the basis for further study on the modulation of intracellular ionic concentrations with the application of ns PEFs and THz electromagnetic fields.