Interactions between DNA and synthetic cationic liposomes

The interaction between T2, T4, T5, T7, and lambda bacteriophages double st randed DNA and cationic liposomes made up of one single synthetic cationic lipid, dioctadecyldimethylammonium bromide (DODAB), is quantitatively evalu ated from a physicochemical point of view. The first step of the interactio n is driven by the electrostatic attraction between DNA and bilayer; with p robes being displaced from their DNA or bilayer sites. Under conditions of DODAB excess, at maximal DODAB adsorption on DNA, there are ca 70 DODAB mol ecules adsorbed per nucleotide on DNA, a molar proportion (MP) that does no t depend on DNA type. Above charge neutralization, there is DNA -induced li posomal rupture, as evaluated from dialysis of DNA/liposome mixtures where liposomes contain [C-14]-sucrose in their internal compartment. In water, t his DNA-induced leakage of radioactive liposomal contents suggests that the interaction DNA/cationic bilayer is not superficial. The DODAB/DNA interac tion led to formation of globules as visualized from dark-field optical mic roscopy and to occurrence of a linear dependence between turbidity for the mixture and 1/lambda(2). At maximal DODAB adsorption, the formation of DODA B/DNA globular complexes causes loss of double-stranded DNA hypochromism as detected from temperature effects on DNA absorbance at 260 nm in the prese nce or absence of DODAB. In summary, the DODAB/DNA interaction is not at al l superficial as expected merely from the electrostatic attraction between oppositely charged molecules: liposome loses its integrity and DNA loses it s double helix becoming single-stranded. The hydrophobic attraction between nitrogenous bases on DNA and hydrocarbon chains on liposome bilayers plays an important role in determining the new physicochemical properties of the complex.