How membrane lipids influence plasma delivery of reactive oxygen species into cells and subsequent DNA damage: an experimental and computational study

• DOI: 10.1039/c9cp03520f
• Publication Date: 2019-08-21T09:36:29Z
• Authors: Jonas Van der Paal; Sung-Ha Hong; Maksudbek Yusupov; Nishtha Gaur; Jun-Seok Oh; Robert D. Short; Endre J. Szili; Annemie Bogaerts
• Keywords: 0301 basic medicine; reactive oxygen and nitrogen species (RONS); diseased cell membranes; 610; Molecular Dynamics Simulation; 530; Reactive Nitrogen Species; 3. Good health; Membrane Lipids; 03 medical and health sciences; Cholesterol; DNA damage; Reactive Oxygen Species; Transport Vesicles; Phospholipids; DNA Damage

The mechanisms of plasma in medicine are broadly attributed to plasma-derived reactive oxygen and nitrogen species (RONS). In order exert any intracellular effects, these RONS must first traverse a major barrier the cell membrane. membrane lipid composition, thereby magnitude this barrier, is highly variable between cells depending on type state (e.g. it widely accepted that healthy cancerous have different compositions). study, we investigate how interactions with components can potentially be exploited future for treatment diseases. We couple phospholipid vesicle experiments, used as simple models, molecular dynamics (MD) simulations provide new insights into interplay phospholipids cholesterol may influence response diseased membranes RONS. focus (i) tail saturation degree, (ii) head group type, (iii) fraction. Using encapsulated probes, study above ingress vesicles, subsequent DNA damage. Our results indicate all enhance or suppress uptake, their relative concentration within Further, show higher uptake vesicles does not always correlate increased damage, which ROS reactivity lifetime. MD multifactorial chemical physical processes at play, including oxidation, packing, rafts formation. methods findings presented here platform knowledge could leveraged development therapies relying action plasma, oxidative stress targeted.