MEMBRANE-FUSION WITH CATIONIC LIPOSOMES - EFFECTS OF TARGET MEMBRANE LIPID-COMPOSITION

Determination of the mechanisms by which cationic liposomes adhere to and fuse with biological membranes is important to understanding how t hese lipid vesicles mediate cellular transfection. To determine what r ole the lipid composition of ''target'' membranes might have in promot ing fusion with cationic liposomes, we have examined the ability of la rge unilamellar vesicles composed of 1,2-dioleoyl-sn-phosphatidylethan olamine (DOPE) and N,N-dimethyl-N,N-di-9-cis-octadecenylammonium chlor ide (DODAC) (1:1) to fuse with target liposomes of varying composition in the absence of DNA. Membrane fusion was promoted by increased nega tive surface charge and, for liquid crystalline lipids, by increased a cyl chain unsaturation in target liposomes. However, the presence of d isaturated phospholipids promoted fusion below the gel to liquid cryst alline transition temperature, an effect which was eliminated by the a ddition of cholesterol. It was also shown that DOPE/DODAC (1:1) LUVs f used with erythrocyte ghosts and that this fusion was blocked by the p resence of serum. Membrane fusion was determined by a quantitative flu orescent lipid mixing assay and qualitatively by freeze-fracture elect ron microscopy and fluorescence microscopy.