Lipid/Detergent Interaction Thermodynamics as a Function of Molecular Shape

In dilute aqueous mixtures of the detergent C12EO8 and the phospholipid POPC the phase and partition behavior as well as the transfer enthalpies of the respective molecules between the various states (monomers, bilayers, micelles) have been measured by isothermal titration calorimetry [Heerklotz et al., J. Phys. Chem. 1996, 100, 6764]. To derive more information about the molecular interpretation of the thermodynamic data, we performed additional experiments for a series of detergents, C12EOn with n ) 3-8 and dependent on temperature (for C12EO8). The data can be discussed in terms of a three-stage model (bilayers, coexistence, micelles) considering nonideal mixing within the aggregates. The mixing properties are determined by packing effects controlling the hydration of the headgroups, the water exposure of the hydrocarbon core, and the order of the hydrocarbon chains. Additionally, two types of systematic deviations from the simple three-stage behavior are found for low n and low detergent contents in the bilayer. These effects could be related to special properties of detergents surrounded by lipids only and to solubilization intermediates occurring close to the lytic detergent content.