Polymorphism of DNA-anionic liposome complexes reveals hierarchy of ion-mediated interactions

Proc Natl Acad Sci U S A. 2005 Aug 9;102(32):11173-8. doi: 10.1073/pnas.0502416102. Epub 2005 Aug 1.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cations, Divalent / chemistry*
  • DNA / chemistry*
  • Genetic Therapy / methods*
  • Liposomes / chemistry*
  • Macromolecular Substances / chemistry*
  • Membranes / chemistry
  • Microscopy, Confocal
  • Models, Molecular*
  • Static Electricity
  • X-Ray Diffraction

Substances

  • Cations, Divalent
  • Liposomes
  • Macromolecular Substances
  • DNA