Structure of DNA-Cationic Liposome Complexes: DNA Intercalation in Multilamellar Membranes in Distinct Interhelical Packing Regimes

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作者：

Radler JO，Koltover I，Salditt T，Safinya CR

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摘要：

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 λ-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 λ-DNA chains form a one-dimensional lattice with distinct interhelical packing regimes. Remarkably, in the isoelectric point regime, the λ-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.

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关键词：

Ammonium Compounds Bacteriophage lambda Cations Chemistry Physical DNA chemistry DNA Viral chemistry Fatty Acids Monounsaturated Isoelectric Point Light Lipid Bilayers Liposomes Microscopy Fluorescence Microscopy Interference Nucleic Acid Conformation Phosphatidylcholines Phosphatidylethanolamines Plasmids Research Support U.S. Gov't Non-P.H.S. Scattering Radiation X-Ray Diffraction