Thermodynamics of the binding of a cationic lipid to DNA

The binding of cationic lipids to DNA induces the condensation of complexes of the lipid and polyelectrolyte. This paper presents data on the binding of the simple cationic lipid cetyltrimethylammonium bromide (CTAB) to DNA prior to the condensation process. The complete thermodynamics of the binding of CTAB to both helical and single strand DNA are evaluated with use of isothermal titration calorimetery data and analysis of UV melting transitions. The binding to the helical form involves a two-step process: first, binding to an isolated phosphate site on the DNA strand with a binding constant of 1.5 x 10(3) M-1, and second, a highly cooperative binding event that seems to involve hydrophobic intereactions between hydrocarbon chains of the bound CTAB. The cooperativity parameter is 56, leading to a cooperative binding constant of 8.7 x 10(4) M-1. The enthalpies of the two binding events on the helix sites are resolved: -20 kJ/mol for the isolated site and +3.3 kJ/mol for contiguous sites. Binding to the single strand DNA is also quite strong with an estimated equilibrium constant of about 1.3 x 10(4) M-1. Because CTAB binds both to helical and single strand DNA, biphasic melting transitions are observed. An analysis of the behavior of the melting curves and the thermodynamic data allows reasonable models of the binding processes to be constructed.