Self-assembled structure of the binary complex of DNA with cationic lipid

Ching Mao Wu, Willisa Liou, Hsin Lung Chen*, Tsang Lang Lin, U. Ser Jeng

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

36 Scopus citations

Abstract

Polyanionic DNA can bind electrostatically with cationic lipid to form the complex exhibiting rich self-assembled structures at various length scales. This class of bioassembly has been considered as a nonviral gene delivery system for gene therapy and as a template for nanostructure construction. The present study reports the self-assembled structure of the binary complex of DNA with a cationic lipid, cholesteryl 3β-N-((dimethylamino)ethyl)carbamate (DC-Chol), in the presence of excess water. Neat DC-Chol self-assembled into cylindrical micelles in aqueous media. These micelles aggregated and fused into multilamellar condensates or vesicles upon complexation with DNA, and the DNA chains confined between the lipid bilayers formed closely packed arrays irrespective of the overall lipid-to-base pair molar ratio. The complexation was found to be a highly cooperative process, where the complexes with nearly 1:1 stoichiometry were formed even when DNA was in excess of DC-Chol in terms of the overall ionic charge. As DC-Chol became in excess, the unbound lipids did not fully macrophase separate from the stoichiometric complex but segregated to form domains coexisting with the bound lipid domains in the lamellae. The presence of these unbound lipid domains reduced the persistence length of the membrane and consequently induced topological transformation of the multilamellar phase from platelike lamellae to circular lamellae observed by TEM at higher DC-Chol composition.

Original languageEnglish
Pages (from-to)4974-4980
Number of pages7
JournalMacromolecules
Volume37
Issue number13
DOIs
StatePublished - 29 06 2004

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