Liquid crystalline phases of dendritic lipid-DNA self-assemblies: Lamellar, hexagonal, and DNA bundles

Alexandra Zidovska, Heather M. Evans, Kai K. Ewert, Joel Quispe, Bridget Carragher, Clinton S. Potter, Cyrus R. Safinya

    Research output: Contribution to journalArticle

    Abstract

    The prospects of gene therapy have generated unprecedented interest in the properties and structures of complexes of nucleic acids (NAs) with cationic liposomes (CLs), which are used as nonviral NA carriers in worldwide clinical trials. An improved understanding of the mechanisms of action of CL-NA complexes is required to enable their widespread therapeutic use. In prior studies of CL-mediated DNA delivery, membrane charge density ( σ M) was identified as a key parameter for transfection efficiency (TE) of lamellar (L α C) CL-DNA complexes. The TE of CL-DNA complexes containing cationic lipids with headgroup valencies from 1+ to 5+ follows a universal bell-shaped curve as a function of σ M. As we report here, the TE of CL-DNA complexes containing new multivalent lipids with dendritic headgroups (DLs) strongly deviates from this curve at high σ M. We have investigated four DLs, MVLG2 (4+), MVLG3 (8+), MVLBisG1 (8+), and MVLBisG2 (16+), in mixtures with neutral 1,2-dioleoyl- sn -glycerophosphatidyl-choline (DOPC). To understand the TE behavior, we have performed X-ray diffraction (XRD), optical microscopy, and cryo- TEM studies of the DL/DOPC mixtures and their DNA complexes. XRD reveals a complex phase behavior of DL-DNA complexes which strongly depends on the headgroup charge. MVLG2(4+)/DOPC-DNA complexes exhibit the lamellar phase at all molar fractions of DL, ΦDL. In stark contrast, MVLBisG2(16+)/ DOPC-DNA complexes remain lamellar only for ΦDL ≤ 0.2. In a narrow regime around ΦDL ) 0.25, the hexagonal phase HI C, consisting of a hexagonal lattice of cylindrical lipid micelles and a DNA honeycomb lattice, is formed. At ΦDL > 0.3, XRD suggests formation of a distorted HI C phase. For ΦDL ≥ 0.5 under high salt conditions, this phase coexists with a bundle phase of DNA condensed by the depletion-attraction effect of DL micelles. The transitions at high σ M from the lamellar phase to the new hexagonal phases of DL-DNA complexes coincide with the deviation from the universal TE behavior of lamellar complexes. The observed high TE, which is independent of σ M, strongly suggests a novel mechanism of action for these DL-DNA complex phases.

    Original languageEnglish (US)
    Pages (from-to)3694-3703
    Number of pages10
    JournalJournal of Physical Chemistry B
    Volume113
    Issue number12
    DOIs
    StatePublished - Mar 26 2009

    Fingerprint

    Self assembly
    Lipids
    bundles
    lipids
    self assembly
    DNA
    deoxyribonucleic acid
    Crystalline materials
    Liposomes
    Liquids
    liquids
    Nucleic acids
    nucleic acids
    Nucleic Acids
    Micelles
    X ray diffraction
    micelles
    diffraction
    gene therapy
    Gene therapy

    ASJC Scopus subject areas

    • Physical and Theoretical Chemistry
    • Materials Chemistry
    • Surfaces, Coatings and Films

    Cite this

    Zidovska, A., Evans, H. M., Ewert, K. K., Quispe, J., Carragher, B., Potter, C. S., & Safinya, C. R. (2009). Liquid crystalline phases of dendritic lipid-DNA self-assemblies: Lamellar, hexagonal, and DNA bundles. Journal of Physical Chemistry B, 113(12), 3694-3703. https://doi.org/10.1021/jp806863z

    Liquid crystalline phases of dendritic lipid-DNA self-assemblies : Lamellar, hexagonal, and DNA bundles. / Zidovska, Alexandra; Evans, Heather M.; Ewert, Kai K.; Quispe, Joel; Carragher, Bridget; Potter, Clinton S.; Safinya, Cyrus R.

    In: Journal of Physical Chemistry B, Vol. 113, No. 12, 26.03.2009, p. 3694-3703.

    Research output: Contribution to journalArticle

    Zidovska, A, Evans, HM, Ewert, KK, Quispe, J, Carragher, B, Potter, CS & Safinya, CR 2009, 'Liquid crystalline phases of dendritic lipid-DNA self-assemblies: Lamellar, hexagonal, and DNA bundles', Journal of Physical Chemistry B, vol. 113, no. 12, pp. 3694-3703. https://doi.org/10.1021/jp806863z
    Zidovska, Alexandra ; Evans, Heather M. ; Ewert, Kai K. ; Quispe, Joel ; Carragher, Bridget ; Potter, Clinton S. ; Safinya, Cyrus R. / Liquid crystalline phases of dendritic lipid-DNA self-assemblies : Lamellar, hexagonal, and DNA bundles. In: Journal of Physical Chemistry B. 2009 ; Vol. 113, No. 12. pp. 3694-3703.
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