Unraveling the Transport Properties of RONS across Nitro-Oxidized Membranes

Abstract

The potential of cold atmospheric plasma (CAP) in biomedical applications has received significant interest, due to its ability to generate reactive oxygen and nitrogen species (RONS). Upon exposure to living cells, CAP triggers alterations in various cellular components, such as the cell membrane. However, the permeation of RONS across nitrated and oxidized membranes remains understudied. To address this gap, we conducted molecular dynamics simulations, to investigate the permeation capabilities of RONS across modified cell membranes. This computational study investigated the translocation processes of less hydrophilic and hydrophilic RONS across the phospholipid bilayer (PLB), with various degrees of oxidation and nitration, and elucidated the impact of RONS on PLB permeability. The simulation results showed that less hydrophilic species, i.e., NO, NO2, N2O4, and O3, have a higher penetration ability through nitro-oxidized PLB compared to hydrophilic RONS, i.e., HNO3, s-cis-HONO, s-trans-HONO, H2O2, HO2, and OH. In particular, nitro-oxidation of PLB, induced by, e.g., cold atmospheric plasma, has minimal impact on the penetration of free energy barriers of less hydrophilic species, while it lowers these barriers for hydrophilic RONS, thereby enhancing their translocation across nitro-oxidized PLB. This research contributes to a better understanding of the translocation abilities of RONS in the field of plasma biomedical applications and highlights the need for further analysis of their role in intracellular signaling pathways.

Effects of Nitro-Oxidative Stress on Biomolecules: Part 1—Non-Reactive Molecular Dynamics Simulations

“…When compared with other studies on the hydroperoxidation of 50% POPC, the nitrated membrane demonstrated similar permeability for hydrophilic species but greater permeability than non-oxidized and hydroperoxidized POPC for hydrophobic species. In a recent MD study, Abduvokhidov et al investigated the transport properties of RONS across membranes with varying degrees of lipid nitro-oxidation [ 185 ]. The results, obtained using US simulations, revealed that certain RONS, namely • NO, • NO 2 , N 2 O 4 , and O 3 , exhibited higher penetration capabilities across both native and nitro-oxidized membranes compared to HNO 3 , s-cis -HONO, s-trans -HONO, H 2 O 2 , HOO • , and • OH.…”

Unraveling the influence of nitration on pore formation time in electroporation of cell membranes: a molecular dynamics simulation approach

“…Surrounding this lipid bilayer are two distinct water phases, one on the top and next on the bottom, each containing 6250 water molecules (for a total of 12 500 water molecules). Diverse model systems were created by altering lipid compositions, specifically 10%, 20%, 30%, and 40% of nitrated DOPC (DOPC-NIT) and native DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine), as depicted in figure 1(b) (see table 1) [44].…”

Enhanced Antimicrobial Activity through Synergistic Effects of Cold Atmospheric Plasma and Plant Secondary Metabolites: Opportunities and Challenges

“…These oxidized products can then react with the cellular components too. In addition, it is also noticed that with CAP, the less hydrophilic species-specifically NO, NO 2 , N 2 O 4 , and O 3 -show greater permeability through lipid bilayers when compared to their hydrophilic counterparts, which include HNO 3 , s-cis-HONO, s-trans-HONO, H 2 O 2 , HO 2 , and OH [69]. In addition to the lipid bilayers, the RONS generated through the synergistic effect of CAP and PSMs can damage the nucleic acid of the DNA present inside the cell.…”