Structures of lipid–DNA complexes: supramolecular assembly and gene delivery

“…These include a lamellar phase in which DNA monolayers are sandwiched between bilayers of neutral and CL, and an inverted hexagonal phase in which the DNA is encapsulated within inverse cylindrical micelles (Radler et al 1997;Koltover et al 1998). The preferred morphology is dependent upon, for example, the chemical nature of the neutral or helper lipids (Safinya 2001). While these studies have provided insights into the structure of these complexes at a molecular level, the process of DNA release from such complexes remains poorly characterized.…”

Section: Introductionmentioning

confidence: 99%

DNA and lipid bilayers: self-assembly and insertion

Khalid

Bond

Holyoake

et al. 2008

J. R. Soc. Interface.

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DNA-lipid complexes are of biomedical importance as delivery vectors for gene therapy. To gain insight into the interactions of DNA with zwitterionic and cationic (dimyristoyltrimethylammonium propane (DMTAP)) lipids, we have used coarse-grained molecular dynamics simulations to study the self-assembly of DPPC and DPPC/DMTAP lipid bilayers in the presence of a DNA dodecamer. We observed the spontaneous formation of lipid bilayers from initial systems containing randomly placed lipids, water-counterions and DNA. In both the DPPC and DPPC/DMTAP simulations, the DNA molecule is located at the water-lipid headgroup interface, lying approximately parallel to the plane of the bilayer. We have also calculated the potential of mean force for transferring a DNA dodecamer through a DPPC/DMTAP bilayer. A high energetic barrier to DNA insertion into the hydrophobic core of the bilayer is observed. The DNA adopts a transmembrane orientation only in this region. Local bilayer deformation in the vicinity of the DNA molecule is observed, largely as a result of the DNA-DMTAP headgroup attraction.

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“…The association of nucleotides and cationic lipids to multimolecular structures is a highly complex process that is poorly understood so far. 41,42 The specific nature of the cationic lipid involved, the presence and sort of helper lipids, the salt conditions and even the sequence of addition of lipids and nucleotides appear to influence the nature of the nucleotide-lipid complexes. Obviously, the charge ratio is also of major importance.…”

Section: Discussionmentioning

confidence: 99%