Molecular dynamics simulations of the permeation and distribution of plasma ROS in aquaporin-1

In recent years, cold atmospheric plasma (CAP) has been found to induce apoptosis selectively in cancer cells and has become a research hotspot, but the underlying mechanisms remain unclear. Aquaporins (AQPs) on the cell membranes of cancer cells are believed to be related to the selective therapeutic mechanism of CAP. In this study, the reactive oxygen species (ROS) generated by CAP, which are believed to play an important role in the apoptosis of cancer cells, crossed the membrane through aquaporin-1 (AQP1). The process of membrane penetration, the distribution of ROS on the membrane, and the free energy barrier of AQP1 on ROS are determined by the molecular dynamics simulation based on the GROMOS 53A6 force field. The ROS distribution shows that the presence of AQP1 results in a deeper distribution of hydrophilic ROS in cell membranes. The free energy barrier for the movement of hydrophilic ROS through AQP1 is significantly lower than that for their movement through the lipid bilayer. Therefore, AQP1 on the cell membrane can improve the efficiency of the entry of hydrophilic ROS into cancer cells. These results illustrate that AQP1 can improve the transmembrane efficiency of ROS and provide insights into the mechanism underlying the selectivity of CAP at the atomic level.