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

Tracy L. Whitehead, Lucretia M. Jones, Rickey P. Hicks

Research output: Contribution to journalArticle

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Abstract

It is well known that neuropeptides interact with lipid vesicles in a manner 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 group has developed a series of anionic micelles (SDS) containing various concentrations of the bile salt CHAPS, which is used as a model for cholesterol. The incorporation of CHAPS into the hydrophobic core of these micelles should 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 results of this study clearly indicate that electrostatic and hydrophobic interactions between the micelle and neuropeptide are completely independent of one another. Increasing the concentration of CHAPS to 15 mM in the micelles blocks the insertion of the hydrophobic side chains of the neuropeptide into the hydrophobic core of the micelles. The electrostatic interactions as determined by diffusion measurements are not affected by the presence of increasing CHAPS concentration. Our observations are consistent with the predictions of Seelig (A. Seelig and J. Seelig, "Interaction of Drugs and Peptides 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).

Original languageEnglish (US)
Pages (from-to)593-605
Number of pages13
JournalBiopolymers
Volume58
Issue number7
DOIs
StatePublished - Jun 11 2001

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Keywords

  • Biological membranes
  • CHAPS
  • Electrostatic interactions
  • Hydrophobic interactions
  • Lipid vesicles
  • Neuropeptide-micelle binding
  • PFG-NMR
  • SDS micelles
  • Secondary structure
  • Substance P
  • Tachykinins

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Biomaterials
  • Organic Chemistry

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