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Nucleic Acids Research Advance Access originally published online on December 22, 2008
Nucleic Acids Research 2009 37(3):849-857; doi:10.1093/nar/gkn1003
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Nucleic Acids Research, 2009, Vol. 37, No. 3 849-857
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Chemistry and Synthetic Biology

Structural analysis of DNA complexation with cationic lipids

Regis Marty1, Christophe N. N'soukpoé-Kossi1, David Charbonneau1, Carl Maximilian Weinert2, Laurent Kreplak2 and Heidar-Ali Tajmir-Riahi1,*

1Department of Chemistry-Biology, University of Québec at Trois-Rivières, C.P. 500, Trois-Rivières (Québec), Canada G9A 5H7 and 2Department of Physics and Atmospheric Science, Sir James Dunn Building, Dalhousie University, Lord Dalhousie Drive, Halifax, Canada NS B3H 3J5

*To whom correspondence should be addressed. Tel: +1 819 376 5011 (ext. 3310); Fax: +1 819 376 5084; Email: tajmirri{at}uqtr.ca

Received November 12, 2008. Revised November 28, 2008. Accepted November 30, 2008.

Complexes of cationic liposomes with DNA are promising tools to deliver genetic information into cells for gene therapy and vaccines. Electrostatic interaction is thought to be the major force in lipid–DNA interaction, while lipid-base binding and the stability of cationic lipid–DNA complexes have been the subject of more debate in recent years. The aim of this study was to examine the complexation of calf-thymus DNA with cholesterol (Chol), 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), dioctadecyldimethylammoniumbromide (DDAB) and dioleoylphosphatidylethanolamine (DOPE), at physiological condition, using constant DNA concentration and various lipid contents. Fourier transform infrared (FTIR), UV-visible, circular dichroism spectroscopic methods and atomic force microscopy were used to analyse lipid-binding site, the binding constant and the effects of lipid interaction on DNA stability and conformation. Structural analysis showed a strong lipid–DNA interaction via major and minor grooves and the backbone phosphate group with overall binding constants of KChol = 1.4 (±0.5) x 104 M–1, KDDAB = 2.4 (±0.80) x 104 M–1, KDOTAP = 3.1 (±0.90) x 104 M–1 and KDOPE = 1.45 (± 0.60) x 104 M–1. The order of stability of lipid–DNA complexation is DOTAP>DDAB>DOPE>Chol. Hydrophobic interactions between lipid aliphatic tails and DNA were observed. Chol and DOPE induced a partial B to A-DNA conformational transition, while a partial B to C-DNA alteration occurred for DDAB and DOTAP at high lipid concentrations. DNA aggregation was observed at high lipid content.


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