Abstract
We report on multi-level atomistic simulations for the interaction of reactive oxygen species (ROS) with the head groups of the phospholipid bilayer, and the subsequent effect of head group and lipid tail oxidation on the structural and dynamic properties of the cell membrane. Our simulations are validated by experiments using a cold atmospheric plasma as external ROS source. We found that plasma treatment leads to a slight initial rise in membrane rigidity, followed by a strong and persistent increase in fluidity, indicating a drop in lipid order. The latter is also revealed by our simulations. This study is important for cancer treatment by therapies producing (extracellular) ROS, such as plasma treatment. These ROS will interact with the cell membrane, first oxidizing the head groups, followed by the lipid tails. A drop in lipid order might allow them to penetrate into the cell interior (e.g., through pores created due to oxidation of the lipid tails) and cause intracellular oxidative damage, eventually leading to cell death. This work in general elucidates the underlying mechanisms of ROS interaction with the cell membrane at the atomic level.
Highlights
We report on multi-level atomistic simulations for the interaction of reactive oxygen species (ROS) with the head groups of the phospholipid bilayer, and the subsequent effect of head group and lipid tail oxidation on the structural and dynamic properties of the cell membrane
The behavior of the ROS in a liquid layer was studied in detail in our previous work by means of classical reactive molecular dynamics (MD) simulations applying the ReaxFF potential[48], and we found that OH, HO2 and H2O2 can travel deep into the water layer and eventually reach the surface of the biomolecule
The only difference is that in our previous work the HO2 radicals reacted with a H2O molecule, forming a superoxide ion (O2−) and a hydrated proton (H3O+), which recombine immediately back to create the reactants again, while this process was not observed in our current density functional-tight binding (DFTB) simulations
Summary
We report on multi-level atomistic simulations for the interaction of reactive oxygen species (ROS) with the head groups of the phospholipid bilayer, and the subsequent effect of head group and lipid tail oxidation on the structural and dynamic properties of the cell membrane. We found that plasma treatment leads to a slight initial rise in membrane rigidity, followed by a strong and persistent increase in fluidity, indicating a drop in lipid order. The latter is revealed by our simulations. This study is important for cancer treatment by therapies producing (extracellular) ROS, such as plasma treatment These ROS will interact with the cell membrane, first oxidizing the head groups, followed by the lipid tails. Several studies showed that CAPs elevate intracellular ROS levels, thereby inducing oxidative damage in cancer cells, which can lead to cell death, i.e., apoptosis[3, 8]. There is a need for more fundamental investigations
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