Jo. Radler et al., STRUCTURE OF DNA-CATIONIC LIPOSOME COMPLEXES - DNA INTERCALATION IN MULTILAMELLAR MEMBRANES IN DISTINCT INTERHELICAL PACKING REGIMES, Science, 275(5301), 1997, pp. 810-814
Cationic liposomes complexed with DNA (CL-DNA) are promising synthetic
ally based nonviral carriers of DNA vectors for gene therapy. The solu
tion structure of CL-DNA complexes was probed on length scales from su
bnanometer to micrometer by synchrotron x-ray diffraction and optical
microscopy. The addition of either linear lambda-phage or plasmid DNA
to CLs resulted in an unexpected topological transition from liposomes
to optically birefringent liquid-crystalline condensed globules. X-ra
y diffraction of the globules revealed a novel multilamellar structure
with alternating lipid bilayer and DNA monolayers. The lambda-DNA cha
ins form a one-dimensional lattice with distinct interhelical packing
regimes. Remarkably, in the isoelectric point regime, the lambda-DNA i
nteraxial spacing expands between 24.5 and 57.1 angstroms upon lipid d
ilution and is indicative of a long-range electrostatic-induced repuls
ion that is possibly enhanced by chain undulations.