Additive action of two or more solutes on lipid membranes

A wide variety of biological processes, pharmaceutical applications, and technical procedures is based on the combined action of two or more soluble compounds to perturb, permeabilize, or lyse biological membranes. Here we present a general model describing the additive action of solutes on the properties of membranes or micelles. The onset and completion of membrane solubilization induced by two surfactants (lauryl maltoside, with nonyl maltoside, octyl glucoside, or CHAPS, respectively) are very well described by our model on the basis of their individual partition coefficients, cmc's, and critical mole ratios R(e)(sat) and R(e)(sol) as detected by isothermal titration calorimetry. This suggests that the thermodynamic phase transition is governed by a single parameter (e.g., spontaneous curvature) in spite of the complexity of structural changes. Such surfactant mixtures show unique features such as nonlinear solubilization boundaries and concentration-dependent effective partition coefficients. Other phenomena such as membrane leakage are predicted to obey additive action if the solutes act via the same mechanism (e.g., toroidal pore formation) but deviate from the model in the case of independent, synergistic, or antagonistic action.