Abstract
In recent years, the ability of cold atmospheric pressure plasmas (CAPS) to selectively induce cell death in cancer cells has been widely established. This selectivity has been assigned to the reactive oxygen and nitrogen species (RONS) created in CAPs. To provide new insights in the search for an explanation for the observed selectivity, we calculate the transfer free energy of multiple ROS across membranes containing a varying amount of cholesterol. The cholesterol fraction is investigated as a selectivity parameter because membranes of cancer cells are known to contain lower fractions of cholesterol compared to healthy cells. We find that cholesterol has a significant effect on the permeation of reactive species across a membrane. Indeed, depending on the specific reactive species, an increasing cholesterol fraction can lead to (i) an increase of the transfer free energy barrier height and width, (ii) the formation of a local free energy minimum in the center of the membrane and (iii) the creation of extra free energy barriers due to the bulky sterol rings. In the context of plasma oncology, these observations suggest that the increased ingress of RONS in cancer cells can be explained by the decreased cholesterol fraction of their cell membrane.
Highlights
Over the last decades, cold atmospheric pressure plasmas (CAPs) have shown great potential in different fields, including, e.g., treatment of chronic wounds, sterilization of living and non-living surfaces or blood coagulation[1,2]
United-atom molecular dynamics simulations were applied to investigate the effect of the cholesterol fraction in cell membranes on the permeation of different reactive oxygen species across these membranes
All potential of mean force (PMF) shown indicate that cholesterol definitely has an influence on the penetration of certain ROS, even for systems without cholesterol, the free energy barriers are still significantly high for species to travel through the membrane, the permeation barrier role of each membrane
Summary
Cold atmospheric pressure plasmas (CAPs) have shown great potential in different fields, including, e.g., treatment of chronic wounds, sterilization of living and non-living surfaces or blood coagulation[1,2]. Due to the similarity of hydrogen peroxide (H2O2 - one of the most important RONS) and water, AQPs are able to facilitate the passive diffusion of this reactive species through the plasma membrane[36], which results in an increased oxidative stress. Wennberg et al used US simulations to investigate the effect of cholesterol on solute (e.g. ammonia, ethanol or benzene) partitioning into different phospholipid bilayer structures by varying the cholesterol concentration, lipid head group and lipid tail saturation[55] One of their most important observations was the correlation between the area per phospholipid and the transfer free energy ΔGw→tails for moving a solute from water into the lipid tail region, which was in line with previous experimental results. CAP treatment is emphasized here due to the observed selectivity (as mentioned above)
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