RT Journal Article SR Electronic T1 Effect of 5-trans isomer of arachidonic acid on model liposomal membranes studied by a combined simulation and experimental approach JF bioRxiv FD Cold Spring Harbor Laboratory SP 279422 DO 10.1101/279422 A1 Ioanna Tremi A1 Dimitrios Anagnostopoulos A1 Ellas Spyratou A1 Paraskevi Gkeka A1 Alexandros G. Georgakilas A1 Chryssostomos Chatgilialoglu A1 Zoe Cournia YR 2018 UL http://biorxiv.org/content/early/2018/03/09/279422.abstract AB Unsaturated fatty acids are found in humans predominantly in the cis configuration. Fatty acids in the trans configuration are primarily the result of human processing (trans fats), but can also be formed endogenously by radical stress. The cis-trans isomerization of fatty acids by free radicals could be connected to several pathologies. Trans fats have been linked to an increased risk of coronary artery disease; however, the reasons for the resulting pathogenesis remain unclear. Here, we investigate the effect of a mono trans isomer of arachidonic acid (C20:4-5trans,8cis,11cis,14cis) produced by free radicals in physiological concentration on a model erythrocyte membrane using a combined experimental and theoretical approach. Molecular Dynamics (MD) simulations of two model lipid bilayers containing arachidonic acid and its 5-trans isomer in 3% mol. were carried out for this purpose. The 5-trans isomer formation in the phospholipids was catalyzed by HOCH2CH2S• radicals, generated from the corresponding thiol by γ-irradiation, in multilamellar vesicles (MLVs) of SAPC. Large unilamellar vesicles were made by the extrusion method (LUVET) as a biomimetic model for cis-trans isomerization. Atomic Force Microscopy and Dynamic Light Scattering were used to measure the average size, morphology, and the z-potential of the liposomes. Both results from MD simulations and experiments are in agreement and indicate that the two model membranes display different physicochemical properties in that the bilayers containing the trans fatty acids were more ordered and more rigid than those containing solely the cis arachidonic acid. Correspondingly, the average size of the liposomes containing trans isomers was smaller than the ones without.