Interactions of cationic lipid vesicles with negatively charged phospholipid vesicles and biological membranes

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Abstract
Lipid vesicles with a positive surface charge have been prepared by using mixtures of phosphatidylethanolamine (PE) and phosphatidylcholine (PC) together with low mole fractions of a cationic lipid analogue, 1,2-bis(oleoyloxy)-3-(trimethylammonio)propane (DOTAP). We have used measurements of vesicle aggregation, lipid mixing, contents mixing, and contents leakage to examine the interactions between these vesicles and similar vesicles that carry a negative surface charge. Mixtures of vesicles with opposite surface charges aggregate readily at physiological or lower ionic strengths, and the extent of this aggregation is enhanced for vesicles that contain high proportions of PE relative to PC. Mixing of lipids and aqueous contents can also be observed between such vesicles, particularly when the vesicles contain substantial proportions of PE. Surprisingly, these latter processes are strongly promoted by monovalent salts and do not proceed at very low ionic strengths. PE/DOTAP vesicles show substantial lipid mixing with negatively charged vesicles containing high proportions of phosphatidylcholine, as well as with human erythrocyte ghosts, on a time scale of a few minutes. These interactions are strongly promoted both by the presence of high levels of PE in the cationic vesicles and by the presence of complementary surface charges on the two membrane populations.