Partitioning of vasoactive intestinal polypeptide into lipid bilayers

Incubation of radiolabeled vasoactive intestinal polypeptide (VIP) with preformed lipid vesicles composed of phosphatidylcholine, phosphatidylglycerol and cholesterol resulted in reversible and saturable association of the peptide with the lipid bilayer. The pH-optimum for the reaction was in the physiological range. The vesicle-associated peptide displayed enhanced stability to proteolytic digestion, it was efficiently released into the supernatant by detergent-solubilization of the vesicles but remained vesicle-associated during treatment with agents that disrupt ionic interactions. Peptide binding by electrically neutral vesicles was lower than that by negative vesicles. Electron spin resonance studies with 5-doxylstearic acid or 16-doxylstearic acid labeled vesicles suggested that VIP decreased the fluidity close to the surface of the bilayer and increased the fluidity in its hydrophobic core. These observations suggest that VIP can bind and penetrate lipid bilayers.