An Inverted Hexagonal Phase of Cationic Liposome-DNA Complexes Related to DNA Release and Delivery

A two-dimensional columnar phase in mixtures of DNA complexed with cationic liposomes has been found in the lipid composition regime known to be significantly more efficient at transfecting mammalian cells in culture compared to the lamellar (LalphaC) structure of cationic liposome-DNA complexes. The structure, derived from synchrotron x-ray diffraction, consists of DNA coated by cationic lipid monolayers and arranged on a two-dimensional hexagonal lattice (HIIC). Two membrane-altering pathways induce the LalphaC --> HIIC transition: one where the spontaneous curvature of the lipid monolayer is driven negative, and another where the membrane bending rigidity is lowered with a new class of helper-lipids. Optical microscopy revealed that the LalphaC complexes bind stably to anionic vesicles (models of cellular membranes), whereas the more transfectant HIIC complexes are unstable and rapidly fuse and release DNA upon adhering to anionic vesicles.