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Fusogenic activity of cationic lipids and lipid shape distribution

Authors :
Michel Vandenbranden
Caroline Lonez
Marc F. Lensink
Jean Marie Ruysschaert
Jean-Marie Vanderwinden
Emilie Kleiren
Source :
Cellular and Molecular Life Sciences. 67:483-494
Publication Year :
2009
Publisher :
Springer Science and Business Media LLC, 2009.

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.

Details

ISSN :
14209071 and 1420682X
Volume :
67
Database :
OpenAIRE
Journal :
Cellular and Molecular Life Sciences
Accession number :
edsair.doi.dedup.....a969d7d377bddeee3af997931feaaeda
Full Text :
https://doi.org/10.1007/s00018-009-0197-x