Effects of the incorporation of CHAPS into SDS micelles on neuropeptide-micelle binding: Separation of the role of electrostatic interactions from hydrophobic interactions

It is well known that neuropeptides interact with lipid vesicles in a manne r similar to biological membranes, with electrostatic interactions between the two providing a mechanism for concentrating the peptide at the vesicle' s surface, followed by hydrophobic interactions between the peptide and the core of the vesicle that induce and stabilize secondary structure motifs. In an effort to understand these interactions to a greater extent, our grou p has developed a series of anionic micelles (SDS) containing various conce ntrations of the bile salt CHAPS, which is used as a model for cholesterol. The incorporation of CHAPS into the hydrophobic core of these micelles sho uld alter the degree to which the neuropeptide can insert itself affecting structure. These interactions were investigated using two-dimensional NMR, pulse-field gradient (PFG) NMR, and molecular modeling experiments. The res ults of this study clearly indicate that electrostatic and hydrophobic inte ractions between the micelle and neuropeptide are completely independent of one another. Increasing the concentration of CHAPS to 15 mM in the micelle s blocks the insertion of the hydrophobic side chains of the neuropeptide i nto the hydrophobic core of the micelles. The electrostatic interactions as determined by diffusion measurements are not affected by the presence of i ncreasing CHAPS concentration. Our observations are consistent with the pre dictions of Seelig (A. Seelig and J. Seelig, "Interaction of Drugs and Pept ides with the Lipid Membrane, in Structure and Function of 7TM Receptors, T . W. Schwartz, S. A. Hjorth, and T. S, Kastrup. Eds., Munksgaard: Location, 1996). (C) 2001 John Wiley & Sons. Inc.