Structure of DNA-Cationic Liposome Complexes: DNA Intercalation in Multilamellar Membranes in Distinct Interhelical Packing Regimes

TLDR

Cationic liposomes complexed with DNA are promising nonviral carriers for gene therapy. The authors examined the solution structure of CL‑DNA complexes across subnanometer to micrometer scales using synchrotron X‑ray diffraction and optical microscopy. Adding λ‑phage or plasmid DNA to the liposomes induces a topological transition to birefringent liquid‑crystalline globules, whose X‑ray diffraction reveals a multilamellar structure of alternating lipid bilayers and DNA monolayers; the λ‑DNA forms a one‑dimensional lattice with interhelical spacings that expand from 24.5 to 57.1 Å at the isoelectric point upon lipid dilution, indicating long‑range electrostatic repulsion possibly enhanced by chain undulations.

Abstract

Cationic liposomes complexed with DNA (CL-DNA) are promising synthetically based nonviral carriers of DNA vectors for gene therapy. The solution structure of CL-DNA complexes was probed on length scales from subnanometer to micrometer by synchrotron x-ray diffraction and optical microscopy. The addition of either linear λ-phage or plasmid DNA to CLs resulted in an unexpected topological transition from liposomes to optically birefringent liquid-crystalline condensed globules. X-ray diffraction of the globules revealed a novel multilamellar structure with alternating lipid bilayer and DNA monolayers. The λ-DNA chains form a one-dimensional lattice with distinct interhelical packing regimes. Remarkably, in the isoelectric point regime, the λ-DNA interaxial spacing expands between 24.5 and 57.1 angstroms upon lipid dilution and is indicative of a long-range electrostatic-induced repulsion that is possibly enhanced by chain undulations.