Fusogenic activity of cationic lipids and lipid shape distribution.
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.
Lonez
Caroline
C
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. clonez@ulb.ac.be
Lensink
Marc F
MF
Kleiren
Emilie
E
Vanderwinden
Jean-Marie
JM
Ruysschaert
Jean-Marie
JM
Vandenbranden
Michel
M
D000818:Animals; D002412:Cations / Q000737:chemistry*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry; D031541:Fluorescence Resonance Energy Transfer; D018014:Gene Transfer Techniques; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D056004:Molecular Dynamics Simulation; D010714:Phosphatidylethanolamines / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry
C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D002412:Cations; D005229:Fatty Acids, Monounsaturated; D008055:Lipids; D008081:Liposomes; D010714:Phosphatidylethanolamines; D000644:Quaternary Ammonium Compounds; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane