Cooperative effects in the interaction between melittin and phosphatidylcholine model membranes. Studies by...

The interaction between the peptide melittin from bee venom with multilamellar liposomes of dipalmitoylphosphatidylcholine or egg yolk phosphatidylcholine has been studied by the method of temperature scanning densitometry, yielding information on the specific volume of the association products and on the changes during the thermotropic transition of the lipids. The effects of the interaction were found to be biphasic with respect to melittin concentration; below 10(-3) mol per mol of phospholipid, an increase in transition temperature, abolition of the pretransition, a reduction in the transition volume of the lipids by about 25%, and a nonadditive increase in apparent specific volume of the complexes were observed. Only minor changes in these parameters could be detected between molar ratios of 10(-3) and 10(-2). Above 1 mol % melittin, the transition temperature decreased and the transition volume approached zero around 10 mol %. Since the effects in the low concentration range cannot be accounted for only by local perturbations around the actual sites of interaction, it is concluded that the interaction involves long range effects of melittin affecting several hundreds of phospholipid molecules. The results are discussed in terms of a phospholipid cluster model, whereby the interaction with melittin leads to a cooperative transition of entire clusters to a state of expanded volume. It is suggested that this transition may be important to the activating effect of melittin on membrane enzymes and to enhanced membrane permeability and lysis.