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The effects of melittin on lipid bilayer assemblies at very low doses, which are important for its toxic action, have been studied. Differential scanning calorimetry indicated that melittin affects the thermotropic behavior of dihexadecylphosphatidylcholine at molar ratios of 10−4. Small-angle X-ray diffraction showed that the structural arrangements are markedly altered. At a melittin/lipid molar ratio of 10−4 the interdigitated structure, which is formed by this lipid below physiological temperatures, is stabilized up to the main-transition temperature (~ 317 K). At higher temperatures a broad continuous transform with superimposed peaks, arising from nonlamellar structures, is observed. At a molar ratio of 10−3 and below the main transition the interdigitated structure represents only a minor fraction. Additionally, the system is very sensitive to swelling. Increasing the water content leads to an increase of the broad continuous transform. Above the main transition a sequence of disordered lamellar→cubic→hexagonal→micellar structure was found in agreement with predictions from general amphiphile/water binary phase diagrams.

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