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Fusogenic activity of cationic lipids and lipid shape distribution

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Abstract

Addition of co-lipids into cationic lipid formulations is considered as promoting cell delivery of DNA by enhancing fusion processes with cell membranes. Here, by combining FRET and confocal microscopy, we demonstrate that some cationic lipids do not require a co-lipid to fuse efficiently with cells. These cationic lipids are able to self-organize into bilayers that are stable enough to form liposomes, while presenting some destabilizing properties reminiscent of the conically shaped fusogenic co-lipid, DOPE. We therefore analyzed the resident lipid structures in cationic bilayers by molecular dynamics simulations, clustering the individual lipid structures into populations of similarly shaped molecules, as opposed to the classical approach of using the static packing parameter to define the lipid shapes. Comparison of fusogenic properties with these lipid populations suggests that the ratio of cylindrical versus conical lipid populations correlates with the ability to fuse with cell membranes.

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Acknowledgments

C.L. is a Postdoctoral Researcher of the Belgian National Fund for Scientific research (FNRS), E.K. is a FRIA (Fonds pour la Formation à la Recherche dans l’Industrie et dans l’Agriculture) fellow, M.F.L. acknowledges support from the Walloon Region of Belgium—DGTRE contract 515993, and M.V. is a Research Associate of the Belgian National Fund for Scientific Research (FNRS). J.M.V. is Research Director of the National Fund for Scientific Research (Belgium) and acknowledges support from the National Fund for Scientific Research (Belgium), Télévie grant 7.4.558.07.F & Fonds de la Recherche Scientifique Médicale, grant 3.4.571.07.F

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Authors and Affiliations

  1. Laboratory for Structure and Function of Biological Membranes, Centre for Structural Biology and Bioinformatics, Faculté des Sciences, Université Libre de Bruxelles, CP 206/2, Campus Plaine, Blvd. du Triomphe, 1050, Brussels, Belgium

    Caroline Lonez, Marc F. Lensink, Emilie Kleiren, Jean-Marie Ruysschaert & Michel Vandenbranden

  2. Laboratory of Neurophysiology, Faculty of Medicine, Université Libre de Bruxelles, Campus Erasme, CP 601, route de Lennik 808, 1070, Brussels, Belgium

    Jean-Marie Vanderwinden

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  1. Caroline Lonez
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  2. Marc F. Lensink
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  3. Emilie Kleiren
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  4. Jean-Marie Vanderwinden
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  5. Jean-Marie Ruysschaert
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  6. Michel Vandenbranden
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Correspondence to Caroline Lonez.

Additional information

C. Lonez and M. F. Lensink contributed equally to this work.

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Lonez, C., Lensink, M.F., Kleiren, E. et al. Fusogenic activity of cationic lipids and lipid shape distribution. Cell. Mol. Life Sci. 67, 483–494 (2010). https://doi.org/10.1007/s00018-009-0197-x

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  • DOI: https://doi.org/10.1007/s00018-009-0197-x

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