Physical–chemical characterization of novel cationic transfection lipids and the binding of model DNA at the air–water interface
Two novel cationic lipids designed for gene transfection were characterized at the air–water interface with respect to their physical–chemical properties and monolayer structures on pH 4 and pH 8 subphases. The binding of model DNA to these monolayers was quantified for the first time by IRRAS, and the structures of the 2D lipoplexes were studied by GIXD and XR. The results have been correlated with 3D structures and with transfection results of former work. The lipids exhibit the same head group structure but differ in their aliphatic chain pattern. While lipid 7 shows strong interactions in the chain and head group region (hydrogen bonds) and forms a highly ordered phase with small cross-sectional areas, the chains of lipid 8 are in the liquid-disordered state on both subphases. The amount of DNA bound to the monolayers of lipids 7 and 8 is comparable at both pH values (considering the same area per molecule) and depends predominantly on the charge density in the monolayer. Surprisingly, even at pH 8 both lipids bind considerable amounts of DNA. Obviously, the approaching macromolecule leads to a further protonation of the lipid monolayer, and in turn more DNA will bind. The interaxial repeat distance of DNA strands is strongly dependent on the phase state of the lipids. While the compression of a liquid-like monolayer (lipid 8) leads to a strong decrease of dDNA, the DNA repeat distances do not change significantly upon compression when adsorbed to a highly charged condensed monolayer (lipid 7).