Thermodynamic analysis of incorporation and aggregation in a membrane: application to the pore-forming peptide alamethicin.

Interaction of the pore-forming antibiotic alamethicin with small unilamellar vesicles of dioleoylphosphatidylcholine has been studied by means of circular dichroism. The data strongly suggest that alamethicin does not bind to the surface of the vesicles but incorporates into the lipid phase to a fairly large extent. Furthermore, aggregation of the peptide in the membrane is apparent from the existence of a 'critical concentration'. Quantitative evaluation and interpretation of the data rest on a quite generally applicable thermodynamic analysis. The underlying phenomenon is treated in terms of a partition equilibrium between the aqueous and lipid media. In the bilayer phase non-ideal interactions (described by appropriate activity coefficients) as well as aggregate formation are considered. Using this approach the relevant parameters of the alamethicin-lipid system have been determined (yielding, in particular, a partition coefficient of 1.3 X 10(3) for the monomeric peptide and a critical aqueous concentration of 2.5 microM). Finally, the possible relevance of these results for the voltage-dependent gating of alamethicin is briefly pointed out.