Jo. Radler et al., STRUCTURE AND INTERFACIAL ASPECTS OF SELF-ASSEMBLED CATIONIC LIPID-DNA GENE CARRIER COMPLEXES, Langmuir, 14(15), 1998, pp. 4272-4283
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.