Polymorphism of DNA–anionic liposome complexes reveals hierarchy of ion-mediated interactions
AUTOR(ES)
Liang, Hongjun
FONTE
National Academy of Sciences
RESUMO
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 nonelectrostatically 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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1183553Documentos Relacionados
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