Reactive Molecular Dynamics Simulation on Interaction Mechanisms of Cold Atmospheric Plasma and Phosphatidylcholine in Cell Membrane Structure

ABSTRACT Cold atmospheric plasma (CAP)‐assisted cancer therapy has garnered significant attention in the field of plasma medicine. The key mechanism involves inducing oxidative stress, which has been proven to be an effective approach for triggering apoptosis in cancer cells, and the reactive oxygen species (ROS) generated by CAP are believed to play a pivotal role in this process. In this study, our focus is on the cell membrane, which serves as the first line of defense for cancer cells, and the primary constituent of the membrane, phosphatidylcholine (POPC), is used as the reaction model. The lipid oxidative stress interaction mechanism of ROS (specifically O atoms, OH radicals, and molecules) with POPC at the molecular level is investigated by reactive molecular dynamics (MD) simulation. The simulation results show that the oxidative processes usually start with H‐abstraction reactions, then are followed by the formation of several biologically functional groups. For instance, fatty acid saturation‐altering double and conjugated dilute bonds, hydrophilic alcohol and aldehyde‐ketone groups, epoxy rings with possible genotoxic impurities, and hydrogen‐bonded receptor cyano. Acrolein, a by‐product of lipid peroxidation, is also observed from the simulation data. The breaking of single bonds, including C‐O, C‐C, and C‐N, is observed in the simulation, as well as the destroying of crucial structural components of POPC, such as the base, glycerophosphate chain, and fatty acid chains, suggesting that the cell membrane structure is disrupted. Compared to the bases and glycerophosphate, the fatty acid chains are most destroyed under the action of ROS. The final oxidation products of POPC have also been revealed from the computational data. Additionally, the dosage effects on the final products are also discussed by adjusting the types and numbers of ROS in the simulation box. This study provides the detailed oxidative process of lipid oxidation of POPC induced by CAP and fundamental insights for optimizing CAP to effectively inactivate cancer cells.