Oxidized Phosphatidylcholines Facilitate Phospholipid Flip-flop in Liposomes

Overview

Journal Biophys J

Publisher Cell Press

Specialty Biophysics

Date 2011 Sep 28

PMID 21943418

Citations 27

Authors

Roman Volinsky

Lukasz Cwiklik

Piotr Jurkiewicz

Martin Hof

Pavel Jungwirth

Paavo K J Kinnunen

Affiliations

Soon will be listed here.

Abstract

Lipid asymmetry is a ubiquitous property of the lipid bilayers in cellular membranes and its maintenance and loss play important roles in cell physiology, such as blood coagulation and apoptosis. The resulting exposure of phosphatidylserine on the outer surface of the plasma membrane has been suggested to be caused by a specific membrane enzyme, scramblase, which catalyzes phospholipid flip-flop. Despite extensive research the role of scramblase(s) in apoptosis has remained elusive. Here, we show that phospholipid flip-flop is efficiently enhanced in liposomes by oxidatively modified phosphatidylcholines. A combination of fluorescence spectroscopy and molecular dynamics simulations reveal that the mechanistic basis for this property of oxidized phosphatidylcholines is due to major changes imposed by the oxidized phospholipids on the biophysical properties of lipid bilayers, resulting in a fast cross bilayer diffusion of membrane phospholipids and loss of lipid asymmetry, requiring no scramblase protein.

Citing Articles

Comprehensive characterization and metabolomics to explore the role of hydrocortisone-induced yin deficiency syndrome in mice.

Jin W, Yang L, Zhang Y, Wang Y, Li Y, Zhao Y Biochem Biophys Rep. 2024; 40:101868.

PMID: 39610834 PMC: 11603011. DOI: 10.1016/j.bbrep.2024.101868.

Methyl-β-cyclodextrin asymmetrically extracts phospholipid from bilayers, granting tunable control over differential stress in lipid vesicles.

Reagle T, Xie Y, Li Z, Carnero W, Baumgart T Soft Matter. 2024; 20(21):4291-4307.

PMID: 38758097 PMC: 11135146. DOI: 10.1039/d3sm01772a.

The Chemical Reactivity of Membrane Lipids.

Duche G, Sanderson J Chem Rev. 2024; 124(6):3284-3330.

PMID: 38498932 PMC: 10979411. DOI: 10.1021/acs.chemrev.3c00608.

Membrane Dynamics and Cation Handling in Ferroptosis.

Hirata Y, Mishima E Physiology (Bethesda). 2024; 39(2):73-87.

PMID: 38193763 PMC: 11283900. DOI: 10.1152/physiol.00029.2023.

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

Ghasemitarei M, Ghorbi T, Yusupov M, Zhang Y, Zhao T, Shali P Biomolecules. 2023; 13(9).

PMID: 37759771 PMC: 10527456. DOI: 10.3390/biom13091371.

References

Sykora J, Jurkiewicz P, Epand R, Kraayenhof R, Langner M, Hof M . Influence of the curvature on the water structure in the headgroup region of phospholipid bilayer studied by the solvent relaxation technique. Chem Phys Lipids. 2005; 135(2):213-21. DOI: 10.1016/j.chemphyslip.2005.03.003. View

Chen R, Yang L, McIntyre T . Cytotoxic phospholipid oxidation products. Cell death from mitochondrial damage and the intrinsic caspase cascade. J Biol Chem. 2007; 282(34):24842-50. PMC: 2701377. DOI: 10.1074/jbc.M702865200. View

van Meer G, Voelker D, Feigenson G . Membrane lipids: where they are and how they behave. Nat Rev Mol Cell Biol. 2008; 9(2):112-24. PMC: 2642958. DOI: 10.1038/nrm2330. View

Angeletti C, Nichols J . Dithionite quenching rate measurement of the inside-outside membrane bilayer distribution of 7-nitrobenz-2-oxa-1,3-diazol-4-yl-labeled phospholipids. Biochemistry. 1998; 37(43):15114-9. DOI: 10.1021/bi9810104. View

Jurkiewicz P, Olzynska A, Langner M, Hof M . Headgroup hydration and mobility of DOTAP/DOPC bilayers: a fluorescence solvent relaxation study. Langmuir. 2006; 22(21):8741-9. DOI: 10.1021/la061597k. View

Leventis P, Grinstein S . The distribution and function of phosphatidylserine in cellular membranes. Annu Rev Biophys. 2010; 39:407-27. DOI: 10.1146/annurev.biophys.093008.131234. View

White S, Wimley W . Hydrophobic interactions of peptides with membrane interfaces. Biochim Biophys Acta. 1998; 1376(3):339-52. DOI: 10.1016/s0304-4157(98)00021-5. View

Fadeel B, Xue D . The ins and outs of phospholipid asymmetry in the plasma membrane: roles in health and disease. Crit Rev Biochem Mol Biol. 2009; 44(5):264-77. PMC: 2787517. DOI: 10.1080/10409230903193307. View

Matsuzaki K, Murase O, Fujii N, Miyajima K . An antimicrobial peptide, magainin 2, induced rapid flip-flop of phospholipids coupled with pore formation and peptide translocation. Biochemistry. 1996; 35(35):11361-8. DOI: 10.1021/bi960016v. View

10.

Simon H, Levi-Schaffer F . Role of reactive oxygen species (ROS) in apoptosis induction. Apoptosis. 2001; 5(5):415-8. DOI: 10.1023/a:1009616228304. View

11.

Higgins J . Biogenesis of endoplasmic reticulum phosphatidylcholine. Translocation of intermediates across the membrane bilayer during methylation of phosphatidylethanolamine. Biochim Biophys Acta. 1981; 640(1):1-15. DOI: 10.1016/0005-2736(81)90527-7. View

12.

Olzynska A, Zan A, Jurkiewicz P, Sykora J, Grobner G, Langner M . Molecular interpretation of fluorescence solvent relaxation of Patman and 2H NMR experiments in phosphatidylcholine bilayers. Chem Phys Lipids. 2007; 147(2):69-77. DOI: 10.1016/j.chemphyslip.2007.03.004. View

13.

Anglin T, Conboy J . Kinetics and thermodynamics of flip-flop in binary phospholipid membranes measured by sum-frequency vibrational spectroscopy. Biochemistry. 2009; 48(43):10220-34. DOI: 10.1021/bi901096j. View

14.

Uhlson C, Harrison K, Allen C, Ahmad S, White C, Murphy R . Oxidized phospholipids derived from ozone-treated lung surfactant extract reduce macrophage and epithelial cell viability. Chem Res Toxicol. 2002; 15(7):896-906. DOI: 10.1021/tx010183i. View

15.

Nakano M, Fukuda M, Kudo T, Matsuzaki N, Azuma T, Sekine K . Flip-flop of phospholipids in vesicles: kinetic analysis with time-resolved small-angle neutron scattering. J Phys Chem B. 2009; 113(19):6745-8. DOI: 10.1021/jp900913w. View

16.

Hess B, Kutzner C, van der Spoel D, Lindahl E . GROMACS 4: Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation. J Chem Theory Comput. 2015; 4(3):435-47. DOI: 10.1021/ct700301q. View

17.

Tanaka Y, Schroit A . Insertion of fluorescent phosphatidylserine into the plasma membrane of red blood cells. Recognition by autologous macrophages. J Biol Chem. 1983; 258(18):11335-43. View

18.

Williamson P, Kulick A, Zachowski A, Schlegel R, Devaux P . Ca2+ induces transbilayer redistribution of all major phospholipids in human erythrocytes. Biochemistry. 1992; 31(27):6355-60. DOI: 10.1021/bi00142a027. View

19.

McIntyre J, Sleight R . Fluorescence assay for phospholipid membrane asymmetry. Biochemistry. 1991; 30(51):11819-27. DOI: 10.1021/bi00115a012. View

20.

Armstrong V, Brzustowicz M, Wassall S, Jenski L, Stillwell W . Rapid flip-flop in polyunsaturated (docosahexaenoate) phospholipid membranes. Arch Biochem Biophys. 2003; 414(1):74-82. DOI: 10.1016/s0003-9861(03)00159-0. View