STRUCTURE AND INTERFACIAL ASPECTS OF SELF-ASSEMBLED CATIONIC LIPID-DNA GENE CARRIER COMPLEXES

Cationic lipid-DNA (CL-DNA) complexes were recently found to exhibit a novel multilamellar structure composed of alternating lipid bilayer a nd DNA monolayer with distinct interhelical DNA spacings (Radler et al . Science 1997, 275, 810). We report on the aggregation behavior, morp hology, and interfacial properties related to the solution structure o f DOPC/DOTAP-DNA complexes. Using optical microscopy and synchrotron X -ray diffraction, we found two discrete regimes for the complex size a nd surface charge as a function of the lipid-to-DNA mass ratio. The re gimes correspond to the coexistence of complexes with either excess DN A or excess liposomes, characterized by a negative and positive surfac e potential of the complexes, respectively. The internal structure in these cases exhibited different but constant DNA packing distances of 35 and 46 Angstrom, respectively. The regimes are separated by a trans ition region around the isoelectric point, where the number of cationi c lipids equals the number of DNA phosphate groups. At the isoelectric point the average complex size diverged and the DNA packing spacing i s described by a simple volume fraction calculation. The complex forma tion occurred on three time scales: rapid condensation, a slower collo idal aggregation, and finally, a long term reorganization or compactio n. Complexes with positive surface charge were shown to adhere to nega tively charged giant liposomes.