On the Interaction of Ionic Detergents with Lipid Membranes Thermodynamic Comparison of n-Alkyl-+N(CH3)3 and n-Alkyl-SO4-

Ionic detergents find widespread commercial applications as disinfectants fungicides or excipients in drug formulations and cosmetics One mode of action is their ease of insertion into biological membranes Very little quantitative information on this membrane-binding process is available to date Using isothermal titration calorimetry (ITC) and dynamic light scattering (DLS) we have made a systematic comparison of the binding of cationic and anionic detergents to neutral and negatively charged lipid membranes The detergents investigated were n-alkyl chains carrying either the trimethylammonium chloride (-N+(CH3)(3)Cl-) or the sodium sulfate (-SO4-Na+) headgroup with chain lengths of n = 10-16 The titration of lipid vesicles into detergent solutions provided the binding enthalpy and the binding isotherm in a model-independent manner At 25 degrees C the membrane binding enthalpies Delta H-mem(0) were small (-0 4 to -4 2 kcal/mol) and showed little correlation with the length of the alkyl chains The ITC binding Isotherms were analyzed in terms of a surface partition model To this purpose, the surface concentration, c(M), of detergent immediately above the plane of binding was calculated with the Gouy-Chapman theory The surface concentration corrects for electrostatic attraction or repulsion and can be larger or smaller than the bulk detergent concentration c(eq) at equilibrium The analysis provides the chemical or hydrophobic binding constant K-D(0) of the detergent and the corresponding free energy The free energies of binding, Delta G(mem)(0), vary between -4 and -10 kcal/mol They show a linear dependence on the chain length which can be used to separate the contributions of the polar group and the hydrocarbon tail in membrane binding The neutral maltose and the cationic N+(CH3)(3) headgroup show stenc repulsion energies of about 2 5 kcal/mol counteracting the hydrophobic binding of the alkyl tail whereas the anionic SO4- headgroup makes almost no contribution to membrane binding The chemical nature of the headgroup influences the packing density of the hydrocarbon chains in the lipid bilayer with N+(CH3)(3) eliciting the weakest chain-chain interaction The minimum repulsive interaction of the SO4- polar group makes the sodium n-alkyl-sulfates much stronger detergents than the nonionic or cationic counterparts, the binding constants K-D(0) being 10-50 times larger than those of the corresponding n-alkyl-trimethylammonium chlorides The membrane insertion was further compared with micelle formation of the same detergent A cooperative aggregation model which includes all possible aggregation states is proposed to analyze micelle formation The partition function can be defined in closed form and it is straightforward to predict the thermodynamic properties of the micellar system When aggregated in micelles the detergent polar groups are in direct interaction and are not separated by lipid molecules Under these conditions the SO4- group exhibits a strong electrostatic repulsive effect of 3 2 kcal/mol while the contributions of the maltose and N+(CH3)(3) headgroups are very similar to those in the lipid bilayer