The interaction between 2'-deoxyadenosine 5'-monophosphate (DMP) and cation
ic liposomes made up of dioctadecyldimethylammonium bromide (DODAB) in wate
r is described. At maximal adsorption, the molar ratio DODAB/DMP is 2:1 and
electrophoretic mobility for the liposomes attains a minimum at a positive
value. At 5 mM ionic strength, maximal DMP adsorption on the liposome beco
mes close to zero, demonstrating that the electrostatic attraction essentia
lly drives the DODAB/DMP complexation. Over the millimolar range of DMP con
centrations (0.4-1.5 mM), upon nucleotide addition, turbidity of the liposo
me dispersion (0.08 mM DODAB) steeply increases as a function of time in co
ntrast with the much smaller flocculation rates upon NaCl addition over a m
uch higher range of NaCl concentrations (40-210 mM NaCl). The nucleotide be
haves as a hydrophobic anion with an affinity for the membrane that is much
higher than that exhibited by a simple anion as chloride. In water, liposo
me electrophoretic mobility decreases as a function of DMP concentration bu
t the liposome/DMP complex remains positively charged, even at the highest
DMP concentrations tested. DMP-induced rupture of liposomes containing [C-1
4]sucrose was evaluated from dialysis of DMP/liposomes mixtures. In water,
DMP-induced leakage of radioactive liposomal contents suggests that the DMP
/bilayer interaction is not superficial. Although the interaction preserves
the positive liposome charge, it does not preserve its integrity. At maxim
al adsorption, DMP insertion in the cationic bilayer is the most reasonable
explanation for the remaining positive charge on the vesicle, the 2:1 DODA
B:DMP molar ratio, and leakage of internal contents from the liposome.