Cationic liposomes complexed with DNA (CL-DNA) are promising synthetically based nonviral carriers of DNA vectors for gene therapy. The solution structure of CL-DNA complexes was probed on length scales from subnanometer to micrometer by synchrotron x-ray diffraction and optical microscopy. The addition of either linear lambda-phage or plasmid DNA to CLs resulted in an unexpected topological transition from liposomes to optically birefringent liquid-crystalline condensed globules. X-ray diffraction of the globules revealed a novel multilamellar structure with alternating lipid bilayer and DNA monolayers. The lambda-DNA chains form a one-dimensional lattice with distinct interhelical packing regimes. Remarkably, in the isoelectric point regime, the lambda-DNA interaxial spacing expands between 24.5 and 57.1 angstroms upon lipid dilution and is indicative of a long-range electrostatic-induced repulsion that is possibly enhanced by chain undulations.

A two-dimensional columnar phase in mixtures of DNA complexed with cationic liposomes has been found in the lipid composition regime known to be significantly more efficient at transfecting mammalian cells in culture compared to the lamellar (LalphaC) structure of cationic liposome-DNA complexes. The structure, derived from synchrotron x-ray diffraction, consists of DNA coated by cationic lipid monolayers and arranged on a two-dimensional hexagonal lattice (HIIC). Two membrane-altering pathways induce the LalphaC --> HIIC transition: one where the spontaneous curvature of the lipid monolayer is driven negative, and another where the membrane bending rigidity is lowered with a new class of helper-lipids. Optical microscopy revealed that the LalphaC complexes bind stably to anionic vesicles (models of cellular membranes), whereas the more transfectant HIIC complexes are unstable and rapidly fuse and release DNA upon adhering to anionic vesicles.

2014I1 a récemment été mis en évidence, en utilisant une méthode de diffraction des rayons X, le rôle prédominant des interactions d'ondulation lors de la dilution par du dodécane d'une phase lamellaire d'un mélange quaternaire lyotrope [1]. Afin d'étudier la compétition entre les interactions d'ondulation et les forces électrostatiques, nous avons étudié l'effet de la dilution avec, soit de l'eau, soit de la saumure (~ 0,5 mole. 1-1 NaCl), sur les interactions d'une phase lamellaire L03B1. Dans ces deux cas, la membrane chargée négativement est composée de Dodecyl Sulfate de Sodium (SDS) et de pentanol. Un montage de rayons X haute résolution, nous permet de mesurer, en fonction de la distance de séparation entre membranes (d), l'exposant ~(d) qui caractérise la loi de puissance du facteur de structure obtenue en rayons X. Cet exposant ~ est directement relié aux interactions entre membranes. Nous avons établi que les interactions électrostatiques à longue portée dominent lors de la dilution par de l'eau. Lors de la dilution par de la saumure, l'adjonction de sel réduit la longueur de Debye (03BBD/d~ 1). Dans ce cas où les interactions électrostatiques sont à courte portée, les interactions d'ondulation dominent de nouveau avec ~(d) = 1,33(1-03B4/d)2 (03B4 est l'épaisseur de la membrane), fonction qui sature à une valeur constante à large distance d conformément aux prédictions de la théorie d'Helfrich [4].

A class of lamellar biological hydrogels comprised of fluid membranes of lipids and surfactants with small amounts of low molecular weight poly(ethylene glycol)-derived polymer lipids (PEG-lipids) were studied by x-ray diffraction, polarized light microscopy, and rheometry. In contrast to isotropic hydrogels of polymer networks, these membrane-based birefringent liquid crystalline biogels, labeled L-alpha,g, form the gel phase when water is added to the liquid-like lamellar L-alpha phase, which reenters a liquid-like mixed phase upon further dilution. Furthermore, gels with larger water content require less PEG-lipid to remain stable. Although concentrated (approximately 50 weight percent) mixtures of free PEG (molecular weight, 5000) and water do not gel, gelation does occur in mixtures containing as little as 0.5 weight percent PEG-lipid. A defining signature of the L-alpha,g regime as it sets in from the fluid lamellar L-alpha phase is the proliferation of layer-dislocation-type defects, which are stabilized by the segregation of PEG-lipids to the defect regions of high membrane curvature that connect the membranes.

The formation kinetics and self-assembly of multilamellar tubules of the diacetylenic phospholipid 1,2-bis(tricosa-10,12-diynoyl)-sn-glycerol-3-phosphocholine formed under controlled cooling rates were studied by x-ray diffraction and optical, atomic force, and scanning electron microscopy. Tubule formation was driven by a reversible first-order phase transition from an intralamellar, chain-melted L(alpha) phase to a chain-frozen L(beta), phase. These observations are the basis of a highly efficient method of tubule production in which tubule lengths can be controlled, between 1 and 100 micrometers, by varying the cooling rate. These tubules can be made in suspensions with 10 percent lipid by mass, far exceeding the lipid solubility limit.