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Effect of 5-trans Isomer of Arachidonic Acid on Model Liposomal Membranes Studied by a Combined Simulation and Experimental Approach

Article
Part of the following topical collections:
  1. Lipid Membranes and Reactions at Lipid Interfaces: Theory, experiments, and applications

Abstract

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 of SAPC. Large unilamellar vesicles were made by the extrusion method (LUVET) as a biomimetic model for cistrans 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.

Keywords

Trans fatty acids Arachidonic acid Liposomes MD simulations 

Notes

Acknowledgements

We acknowledge computational time granted from the Greek Research & Technology Network (GRNET) in the National HPC facility – ARIS under project ID pr001026-MAG-NANO-MEM. We also acknowledge Dr. Eleni Efthimiadou for providing us the Zetasizer for the Dynamic Light Scattering experiments and Giorgia Giacometti for her ancillary help in the liposome preparation. ZC was co-funded by the European Commission under the H2020 Research Infrastructures Contract No. 675121 (Project VI-SEEM). All data is available to download at: https://repo.vi-seem.eu/handle/21.15102/VISEEM-313.

Compliance with Ethical Standards

Conflict of interest

All authors declare that they have no conflict of interest.

Research Involving Human and Animal Participants

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

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Supplementary material 1 (PDF 2047 KB)

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Authors and Affiliations

  1. 1.DNA Damage Laboratory, Department of Physics, School of Applied Mathematical and Physical SciencesNational Technical University of Athens (NTUA)AthensGreece
  2. 2.Biomedical Research Foundation Academy of AthensAthensGreece
  3. 3.Institute of Nanoscience and Nanotechnology (INN)N.C.S.R. DemokritosAthensGreece
  4. 4.ISOFConsiglio Nazionale delle RicercheBolognaItaly
  5. 5.GlaxoSmithKlineAthensGreece
  6. 6.Structure Design and InformaticsSanofiChilly-MazarinFrance

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