Physico-chemical aspects of the interaction between DNA and oppositely charged mixed liposomes

The mechanism of complex formation be tween DNA and oppositely charged dioc tadecyldimethylammonium bromide/dioleoyl phosphatidylethanolamine (DODAB/DO PE) and 1,2-dioleoyl-3-trimethylammonium propane (DOTAP)/DOPE mixed liposom es, as well as the physico-chemical properties of DNA-mixed liposome comple xes, were examined. Fluorescence microscopy showed that the interaction bet ween DNA and oppositely charged mixed liposomes started at very low liposom e concentrations and induced a discrete coil-globule transition in individu al DNA molecules. The DNA size distribution was bimodal in a wide range of liposome concentrations. The critical concentration of the cationic lipid n eeded for the complete compaction of single DNA molecules depended on the c omposition of the charged mixed DODAB/DOPE and DOTAP/DOPE liposomes. Cryoge nic transmission electron microscopy (cryo-TEM) observations of DNA complex es with mixed liposomes revealed that the lamellar packing of lipid molecul es was typical for the complexes formed from the cationic lipid-enriched mi xtures, while inverted hexagonal arrays were found for the neutral lipid-en riched complexes. The microstructures of the complexes were also examined w ith the use of the small-angle X-ray scattering (SAXS) technique, which con firmed the results obtained by cryo-TE microscopy and enabled the quantitat ive characterization of lipid packaging in the complexes with DNA macromole cules. We also found that the introduction of the neutral lipid into the co mplexes between DNA and oppositely charged lipids, DODAB and DOTAP, moderat ely increased the thermal stability of the complexes and changed the quanti tative characteristics of the melting profiles of the complexes. (C) 1999 E lsevier Science B.V. All rights reserved.