Phase Diagram, Stability, and Overcharging of Lamellar Cationic Lipid–DNA Self-Assembled Complexes

Cationic lipid–DNA (CL-DNA) complexes comprise a promising new class of synthetic nonviral gene delivery systems. When positively charged, they attach to the anionic cell surface and transfer DNA into the cell cytoplasm. We report a comprehensive x-ray diffraction study of the lamellar CL-DNA self-a...

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Bibliographic Details
Published inBiophysical journal Vol. 77; no. 2; pp. 915 - 924
Main Authors Koltover, I., Salditt, T., Safinya, C.R.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 01.08.1999
Biophysical Society
Subjects
Biophysical Phenomena
Biophysics
Cations
Deoxyribonucleic acid
DNA
DNA - administration & dosage
DNA - chemistry
DNA - genetics
Drug Carriers
Drug Stability
Gene Transfer Techniques
Lipids
Liposomes - chemistry
Macromolecular Substances
Models, Molecular
Molecular biology
Static Electricity
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Summary:Cationic lipid–DNA (CL-DNA) complexes comprise a promising new class of synthetic nonviral gene delivery systems. When positively charged, they attach to the anionic cell surface and transfer DNA into the cell cytoplasm. We report a comprehensive x-ray diffraction study of the lamellar CL-DNA self-assemblies as a function of lipid composition and lipid/DNA ratio, aimed at elucidating the interactions determining their structure, charge, and thermodynamic stability. The driving force for the formation of charge-neutral complexes is the release of DNA and lipid counterions. Negatively charged complexes have a higher DNA packing density than isoelectric complexes, whereas positively charged ones have a lower packing density. This indicates that the overcharging of the complex away from its isoelectric point is caused by changes of the bulk structure with absorption of excess DNA or cationic lipid. The degree of overcharging is dependent on the membrane charge density, which is controlled by the ratio of neutral to cationic lipid in the bilayers. Importantly, overcharged complexes are observed to move toward their isoelectric charge-neutral point at higher concentration of salt co-ions, with positively overcharged complexes expelling cationic lipid and negatively overcharged complexes expelling DNA. Our observations should apply universally to the formation and structure of self-assemblies between oppositely charged macromolecules.
ISSN:0006-3495
1542-0086
DOI:10.1016/S0006-3495(99)76942-0