Research On The Mechanism Of Selective Apoptosis Of Active Particles In Plasma

Cold atmospheric plasma(CAP)is widely used in many fields,such as chemical engineering,aerospace,biomedicine and material surface treatment,due to its strong chemical activity,variable operating parameters and simple generation mode.In recent years,because a variety of active particles contained in CAP can interact with biological macromolecules,its application in the biomedical field has been highly valued,especially in the field of cancer treatment.Although a large number of studies have verified the effectiveness of CAP in the treatment of cancer in experiments,the microscopic mechanism of CAP selective apoptosis of cancer cells remains unclear due to the limitations of detection methods.As a research method,molecular dynamics simulation can be used to analyze and explore the microscopic mechanism of interaction between active particles and cancer cells in atmospheric low-temperature plasma.With the help of a high-performance computer,we will simulate the microscopic process of multiple active particles in caps crossing the cell membrane of cancer cells under different conditions,and analyze the interactions between the active particles and various substances in the cell membrane.This will contribute to the improvement of cap-selective apoptosis theory and provide guidance for the experimental and clinical application of CAP.The main content of this paper includes the following aspects:(1)The application of CAP in the field of biomedicine was reviewed,and the research status of CAP in the treatment of cancer was integrated and analyzed,as well as the reasons for its selective apoptosis of cancer cells were summarized.This paper introduces the application of molecular dynamics simulation in biomedicine and demonstrates its feasibility in analyzing membrane permeation process of active particles.Two cell membrane models were modeled by PACKMOL software and further analyzed by molecular dynamics simulation.(2)Molecular dynamics simulation was used to study the distribution and permeability process of ROS(OH,HO2,H2O2,O2)of different species at the membrane water interface,and the changes of membrane morphology and permeability were studied at the microscopic level.Concentration affects the distribution of ROS at the membrane-water interface,thereby affecting the probability of contact with phospholipids,cholesterol,and the efficiency of plasma destruction of the cell membranes.The hydrophobic O2 molecules easily penetrate into the bilayer membrane and remain inside and have the highest probability of contact with the unsaturated region of the phospholipid,thus playing the most important role in oxidation.The double bond region of cholesterol is most susceptible to oxidation by HO2.The ROS in the head region of the phospholipid cause the thickness of the cell membrane to decrease,and the ROS inside the bilayer membrane cause an alignment between the phospholipids,thereby increasing the membrane area.Under natural conditions.The hydrophobic molecule(O2)is most likely to enter the interior of the cell,while the bilayer membrane has a strong barrier to hydrophilic molecules(OH,HO2,H2O2).Among them,H2O2 has the highest transmembrane barrier energy due to hydrogen bonding,while OH and HO2 are basically the same.Under plasma treatment,the transmembrane energy of HO2 decreases significantly,while the other types of ROS did not considerably change.(3)Molecular dynamics simulation was used to analyze the distribution and osmotic behavior of reactive oxygen species produced by low temperature plasma at atmospheric pressure in the cell membrane containing aquaporin-1.The effects of these ROS on the conformation of AQP1 during the transmembrane process were studied to further understand their effects on the transport function of AQP1.ROS generated by CAP could cross the membrane through AQP1,and this method is more efficient than the transmembrane via the lipid bilayer.The free energy barriers of OH and HO2 through the water channel formed by AQP1 are similar,which are obviously lower than that of H2O2.In the transmembrane process,ROS generated by CAP will affect the conformation of AQP1,which is mainly caused by changes in solvent properties.Most H2O2 is distributed in the aqueous phase,and the change in solvent properties near AQP1 is less.OH and HO2 greatly influence the solvent properties of both ends of the water channel.Hydrophobic O2 molecules are directly distributed in the interior of AQP1 without changing the solvent to affect its conformation and function.This conclusion provides guidance for the selection of plasma dose(ionization time and treatment time)in plasma medicine,so as to promote the further development of CAP application in experiment and clinic.