title: Polymorphism of DNA-anionic liposome complexes reveals hierarchy of ion-mediated interactions.
abstract: Self-assembled DNA delivery systems based on anionic lipids (ALs) complexed with DNA mediated by divalent cations have been recently introduced as an alternative to cationic lipid-DNA complexes because of their low cytotoxicity. We investigate AL-DNA complexes induced by different cations by using synchrotron small angle x-ray scattering and confocal microscopy to show how different ion-mediated interactions are expressed in the self-assembled structures and phase behavior of AL-DNA complexes. The governing interactions in AL-DNA systems are complex: divalent ions can mediate strong attractions between different combinations of the components (such as DNA-DNA and membrane-membrane). Moreover, divalent cations can coordinate non-electrostatically with lipids and modify the resultant membrane structure. We find that at low membrane charge densities AL-DNA complexes organize into a lamellar structure of alternating DNA and membrane layers crosslinked by ions. At high membrane charge densities, a new phase with no analog in cationic lipid-DNA systems is observed: DNA is expelled from the complex, and a lamellar stack of membranes and intercalated ions is formed. For a subset of the ionic species, high ion concentrations generate an inverted hexagonal phase comprised of DNA strands wrapped by ion-coated lipid tubes. A simple theoretical model that takes into account the electrostatic and membrane elastic contributions to the free energy shows that this transition is consistent with an ion-induced change in the membrane spontaneous curvature, c0. Moreover, the crossover between the lamellar and inverted hexagonal phases occurs at a critical c0 that agrees well with experimental values.
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Liang
authors.forename: Daniel
authors.initials: D
authors.lastname: Harries
authors.forename: Gerard C L
authors.initials: GC
authors.lastname: Wong
mesh_terms: D002413:Cations, Divalent / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D015316:Genetic Therapy / Q000379:methods*; D008081:Liposomes / Q000737:chemistry*; D046911:Macromolecular Substances / Q000737:chemistry*; D008566:Membranes / Q000737:chemistry; D018613:Microscopy, Confocal; D008958:Models, Molecular; D055672:Static Electricity; D014961:X-Ray Diffraction
chemical_list: D002413:Cations, Divalent; D008081:Liposomes; D046911:Macromolecular Substances; D004247:DNA