Lipid-DNA Complex Formation: Reorganization and Rupture of Lipid Vesicles in the Presence of DNA As Observed by Cryoelectron Microscopy

Huebner, Sebastian; Battersby, Bronwyn J.; Grimm, Rudo; Cevc, Gregor

doi:10.1016/s0006-3495(99)77467-9

Cited by 198 publications

(211 citation statements)

References 22 publications

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“…As DNA is added to the vesicle solution, small complexes start to form at low concentrations; at slightly higher DNA concentrations they begin to aggregate forming larger clusters, as noted from the maximum in x c>300 nm × 300 nm for R = 1. Cluster formation at electroneutrality has been seen previously in systems of hydrophobically modified polyelectrolytes/oppositely charged surfactants [53], on DNA/cationic liposomes [8,44,55,56] as well as in Monte Carlo simulations of polyelectrolyte-macroion solutions [54]. Above this isoelectric point, the clusters start to become smaller and the complexes begin drifting apart from each other, due to electrostatic repulsions generated by the excess of negative charges in the structures.…”

Section: Structure Of the Solution Complexesmentioning

confidence: 57%

The association of DNA and stable catanionic amino acid-based vesicles

Rosa

Morán

Miguel

et al. 2007

Colloids and Surfaces A: Physicochemical and Engineering Aspect

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Cationic surfactants associate strongly to DNA and compact but are often toxic. The interaction of some novel cationic amino acid-based surfactants, which may enhance transfection and appear to be nontoxic, is described. A cationic arginine-based surfactant, ALA, gives in combination with anionic surfactants spontaneously stable vesicles, and special attention is given to the association of these catanionic vesicles, with a net positive charge, to DNA. The ability of this surfactant alone to compact DNA is compared in fluorescence microscopy studies to classical cationic surfactants. Addition of DNA to a solution of the catanionic vesicles results in associative phase separation at very low vesicle concentrations; there is a separation into a precipitate and a supernatant solution, which is first bluish but becomes clearer as more DNA is added. From studies using cryogenic transmission electron microscopy (cryo-TEM) and small angle X-ray scattering it is demonstrated that there is a lamellar structure with DNA arranged within the surfactant bilayers. Analysis of the supernatant by means of proton nuclear magnetic resonance ( 1 H NMR) showed that above the isoelectric point between ALA, anionic surfactant (sodium octyl sulfate, SOS) and DNA, anionic surfactant starts to be expelled from the bilayers on further incorporation of DNA. There appears to be a transition from a lamellar to a hexagonal liquid crystal structure when most of SOS has been expelled from the aggregate bilayers; at higher DNA-to-surfactant ratios, self-assembled SOS micelles and the excess of DNA added seem to coexist in solution. Regarding the phase-separating DNA-surfactant particles, cryo-TEM demonstrates a large and nonmonotonic variation of particle size as the DNA-surfactant ratio is varied, with the largest particles obtained in the vicinity of overall charge neutrality.

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Section: Structure Of the Solution Complexesmentioning

confidence: 57%

The association of DNA and stable catanionic amino acid-based vesicles

Rosa

Morán

Miguel

et al. 2007

Colloids and Surfaces A: Physicochemical and Engineering Aspect

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“…Multilamellar lipid -DNA complexes appear to form by mechanism that involves the rupture of an approaching vesicle and subsequent adsorption of its membrane to a "template" vesicle or a lipid-DNA complex. The authors [33] do not exclude also another mechanism, when the attached vesicle is flattened, and is adsorbed to a "template" vesicle. However, in this way, the complex grows always with even number of layers.…”

Section: Kinetics Of C 12 No/dope/dna Complex Formation Followed By Sansmentioning

confidence: 92%

“…The number of layers increases gradually, and about ~ 4 additional layers were attached during the followed time interval. Cryoelectron microscopy observations [33] report that most likely the DNA -cationic liposomes complex growth begins with one DNA -coated vesicle. In this way DNA acts as a molecular "glue" enforcing close apposition of neighbour vesicle.…”

Section: Kinetics Of C 12 No/dope/dna Complex Formation Followed By Sansmentioning

confidence: 99%

“…In spite of high polydispersity (~ 43 %), to accommodate DNA with a diameter ~ 25 Å into a lamellar phase with spacing ~ 59 Å would suppose thinning of the lipid bilayer. As mentioned above, one of mechanisms of the complexes growth supposes an adsorption of flattened vesicles to a "template" vesicle [33]. In this way, the complex grows always with even number of layers.…”

Section: Kinetics Of C 12 No/dope/dna Complex Formation Followed By Sansmentioning

confidence: 99%

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Lipid based drug delivery systems: Kinetics by SANS

Uhrı́ková

Teixeira

Hubčík

et al. 2017

J. Phys.: Conf. Ser.

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Abstract. N,N-dimethyldodecylamine-N-oxide (C 12 NO) is a surfactant that may exist either in a neutral or protonated form depending on the pH of aqueous solutions. Using small angle Xray diffraction (SAXD) we demonstrate structural responsivity of C 12 NO/dioleoylphosphatidylethanolamine (DOPE)/DNA complexes designed as pH sensitive gene delivery vectors. Small angle neutron scattering (SANS) was employed to follow kinetics of C 12 NO protonization and DNA binding into C 12 NO/DOPE/DNA complexes in solution of 150 mM NaCl at acidic condition. SANS data analyzed using paracrystal lamellar model show the formation of complexes with stacking up to ~32 bilayers, spacing ~ 62 Å, and lipid bilayer thickness ~37 Å in 3 minutes after changing pH from 7 to 4. Subsequent structural reorganization of the complexes was observed along 90 minutes of SANS mesurements.

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“…A useful starting point is the physics governing the analogous CL-DNA complexes (7,(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). DNA and CLs self-assemble into condensed multilamellar complexes, where parallel DNA chains are confined between lipid sheets (14,15).…”

mentioning

confidence: 99%

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

Liang

Harries

Wong

2005

Proc. Natl. Acad. Sci. U.S.A.

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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 selfassembled 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, c 0. Moreover, the crossover between the lamellar and inverted hexagonal phases occurs at a critical c0 that agrees well with experimental values.colloids ͉ like-charge attraction ͉ membrane ͉ self-assembly ͉ x-ray G ene therapy using either viral or synthetic vectors is currently one of the most promising strategies for developing cures for many hereditary and acquired diseases. Protocols have been approved for cancer, hemophilia, cystic fibrosis, neuromuscular disorders, and others (1). Although synthetic nonviral systems such as cationic liposomes generally transfect less efficiently than viruses, they have a number of advantages, such as high DNA packaging capacity and low immunogenicity. Cationic lipid (CL)-DNA complexes have emerged as one of the major nonviral DNA delivery platforms (1-7) and have been used to transfect a broad range of cell types and to deliver to cancer vaccines (8-10).Anionic lipids (ALs) occur naturally in eukaryotic cell membranes, and DNA delivery systems based on ALs have recently been examined as an alternative to CLs because of their low cytotoxicity (11-13). ALs can be complexed with anionic DNA via interaction with multivalent cations such as Ca 2ϩ and have been shown to successfully transfer oligonucleotides. An outstanding problem of this approach is the inefficient association between the ALs and DNA molecules, which is attributed to their like-charge electrostatic repulsion.Rational design of AL-DNA vectors requires a coherent understanding of...

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Lipid-DNA Complex Formation: Reorganization and Rupture of Lipid Vesicles in the Presence of DNA As Observed by Cryoelectron Microscopy

Cited by 198 publications

References 22 publications

The association of DNA and stable catanionic amino acid-based vesicles

The association of DNA and stable catanionic amino acid-based vesicles

Lipid based drug delivery systems: Kinetics by SANS

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

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