Direct Evidence for Counterion Release upon Cationic Lipid−DNA Condensation

Wagner, Kathrin; Harries, Daniel; May, Sylvio; Kahl, Valentin; Rädler, and J. O.; Ben‐Shaul, Avinoam

doi:10.1021/la991268a

Cited by 171 publications

(203 citation statements)

References 11 publications

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“…36−38 In those instances, condensation due to electrostatic interactions persists up to charge neutrality. 39 Figure 6A For simplicity, we consider PS lipid valence to be one free negative charge, and assume that the valence of MBP (Z) is determined by the total amino acid charge at pH 7.4 (i.e., Z = +21.1). This assumption overestimates Z, as some amino acids may not be exposed to lipids and ions within the intermembrane spacing.…”

Section: Articlementioning

confidence: 99%

Structural Transition in Myelin Membrane as Initiator of Multiple Sclerosis

et al. 2016

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ABSTRACT:In demyelinating diseases such as multiple sclerosis, disrupted myelin structures impair the functional role of the sheath as an insulating layer for proper nerve conduction. Though the etiology and recovery pathways remain unclear, in vivo studies show alterations in the lipid and the adhesive protein (myelin basic protein, MBP) composition. We find that in vitro cytoplasmic myelin membranes with modified lipid composition and low MBP concentration, as in demyelinating disease, show structural instabilities and pathological phase transition from a lamellar to inverted hexagonal, which involve enhanced local curvature. Similar curvatures are also found in vivo in diseased myelin sheaths. In addition, MBP dimers form a correlated mesh-like network within the inner membrane space, only in the vicinity of native lipid composition. These findings delineate the distinct functional roles of dominant constituents in cytoplasmic myelin sheaths, and shed new light on mechanisms disrupting lipid−protein complexes in the diseased state.

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Section: Articlementioning

confidence: 99%

Structural Transition in Myelin Membrane as Initiator of Multiple Sclerosis

et al. 2016

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“…The electrostatic energy F elec can be evaluated by using a full free energy calculation based on the Poisson-Boltzmann equation as described (23,28). In the following we set the charging free energy for the lamellar complex to zero in a relative scale and measure that of the hexagonal complex with respect to it.…”

Section: Modelmentioning

confidence: 99%

“…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%

“…By lowering the membrane's bending rigidity or changing its spontaneous curvature, an inverted hexagonal phase with an enhanced tendency for membrane fusion can be formed, in which DNA chains coated by lipid monolayers are packed into a 2D columnar hexagonal array (15). In these self-assembled complexes, the CL head groups neutralize the phosphate groups on the DNA chains, effectively releasing the counterions previously bound electrostatically to lipids and DNA, thus gaining translational entropy (23). The pioneering studies have shown that physical parameters, such as self-assembled nanostructure and membrane charge density, are crucial elements in transfection efficiency (31).…”

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confidence: 99%

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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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“…Studies on the interaction between DNA and lipid-based vesicles have for a long time been presented in the literature whereas studies on mixtures of catanionic vesicles and DNA are more recent [7][8][9]. Nevertheless, they all present a similar feature, a strong associative phase separation with precipitate formation [8]; the driving force for this strong association is the counterion release [10].…”

Section: Introductionmentioning

confidence: 99%

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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Direct Evidence for Counterion Release upon Cationic Lipid−DNA Condensation

Cited by 171 publications

References 11 publications

Structural Transition in Myelin Membrane as Initiator of Multiple Sclerosis

Structural Transition in Myelin Membrane as Initiator of Multiple Sclerosis

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

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

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