Structure and phase transformation of oligodeoxynucleotide/lipid lipoplexes on solid supports

Lipoplexes are composed of lipids and nucleic acids and have an ordered multilamellar structure with a periodic 1D array of parallel nucleic acid strands in the lipid bilayers. We report a low-angle X-ray diffraction study on solid-supported lipoplex films composed of synthetic single-stranded oligodeoxynucleotides (ssODN) and lipids. The ssODN molecules distribute sparsely in the headgroup regions when the weight concentration of the ssODN in the lipoplex is low. The lipoplex separates into two phases, an ODN-poor phase and an ODN-rich phase, when the weight concentration of the ssODN is increased beyond a level at which the ssODN molecules contact each other so that some regions of the lipid bilayers must accommodate two layers of the ssODN. The phase separation is a result of the fusion of such regions to minimize the total interfacial energy of the system. The ssODN molecules distort the lipid bilayers in the ODN-poor phase. The local area per lipid molecule is increased by the distortions so that the interbilayer distance of the lipoplex film is smaller than that of the lipid film without the ssODN. The ODN-rich phase has a much larger interbilayer distance because two layers of ssODN are intercalated into each lipid bilayer. The ssODN molecules are tightly compacted, and the lipid bilayers are not distorted in the ODN-rich phase.