Effect of micellar charge on the conformation and dynamics of melittin

Abstract Electrostatic interactions play a crucial role in modulating and stabilizing molecular interactions in membranes and membrane-mimetic systems such as micelles. We have monitored the change in the confor-mation and dynamics of the cationic hemolytic peptide melittin bound to micelles of various charge types, uti-lizing fluorescence and circular dichroism (CD) spec-troscopy. The sole tryptophan of melittin displays a red-edge excitation shift (REES) of 3–6 nm when bound to anionic, nonionic, and zwitterionic micelles. This suggests that melittin is localized in a restricted envi-ronment, probably in the interfacial region of the mi-celles, and this region offers considerable restriction to the reorientational motion of the solvent dipoles around the excited state tryptophan in melittin. Further, the rotational mobility of melittin is considerably reduced in these micelles and is found to be dependent on the sur-face charge of micelles. Interestingly, our results show that melittin does not partition into cetyltrimethylam-monium bromide (CTAB) micelles owing to electrostatic repulsion between melittin and CTAB micelles, both of which carry a positive charge. In addition, the fluores-cence lifetime of melittin is modulated in micelles of different charge types. The lowest mean fluorescence lifetime is observed in the case of melittin bound to anionic sodium dodecyl sulfate (SDS) micelles. CD spectroscopy shows that micelles induce significant he-licity to melittin, with maximum helicity being induced in the case of melittin bound to SDS micelles. Fluores-cence quenching measurements using the neutral aque-ous quencher acrylamide show differential accessibility of melittin in various types of micelles. Taken together, our results show that micellar surface charge can mod-ulate the conformation and dynamics of melittin. These results could be relevant to understanding the role of the surface charge of membranes in the interaction of membrane-active, amphiphilic peptides with mem-branes