Thermodynamics of lipid-peptide interactions.

This review is focused on peptide molecules which exhibit a limited solubility in the aqueous phase and bind to the lipid membrane from the aqueous medium. Surface adsorption, membrane insertion, and specific binding are usually accompanied by changes in the heat content of the system and can be measured conveniently with isothermal titration calorimetry, avoiding the necessity of peptide labeling. The driving forces for peptide adsorption and binding are hydrophobicity, electrostatics, and hydrogen bonding. An exclusively hydrophobic interaction is exemplified by the immunosuppressant drug cyclosporine A. Its insertion into the membrane can be described by a simple partition equilibrium X(b)=K(0)C(eq). If peptide and membrane are both charged, electrostatic interactions are dominant leading to nonlinear binding curves. The concentration of the peptide near the membrane interface can then be much larger than its bulk concentration. Electrostatic effects must be accounted for by means of the Gouy-Chapman theory before conventional binding models can be applied. A small number of peptides and proteins bind with very high affinity to a specific lipid species only. This is illustrated for the lantibiotic cinnamycin (Ro 09-0198) which forms a 1:1 complex with phosphatidyethanolamine with a binding constant of 10(8) M(-1). Membrane adsorption and insertion can be accompanied by conformational transitions facilitated, in part, by hydrogen bonding mechanisms. The two membrane-induced conformational changes to be discussed are the random coil-to-alpha-helix transition of amphipathic peptides and the random coil-to-beta-structure transition of Alzheimer peptides.