Poster Presentation 2014 International Biophysics Congress

Dielectric constant and water penetration gradients along transmembrane peptide-lipid bilayer interface (#602)

Tatyana Smirnova 1 , Matthew Donohue 1 , Maxim A. Voynov 1 , Alex Smirnov 1
  1. North Carolina State University, Raleigh, NC, USA

Polarity, electric potentials, and hydration are the major physico-chemical characteristics of lipid membranes that govern membrane-protein and protein-protein interactions as well as small molecules transport. In this work we report on employing pH-sensitive ionizable EPR labels to profile a heterogeneous dielectric environment along the α-helix of a WALP peptide integrated in a lipid bilayer.  Labels were attached to two cysteine residues positioned equidistant from the center of the peptide so that the primary sequence of each peptide is palindromic, thus insuring symmetric location of the labels with respect to the bilayer center. The change in protonation state of the nitroxide was directly observed by EPR.  Q-band double electron-electron resonance (DEER) experiments were carried out to determine the distance between spin labels when imbedded in lipid bilayers to provide information about the label location.  Thus, for the first time measurements of local electrostatics at peptide-bilayer interface were based on direct distance measurements rather than on assumptions on the probe location.  Two pH sensitive spin labels, methanethiosulfonic acid S-(1-oxyl-2,2,3,5,5-pentamethyl-imidazolidin-4-ylmethyl) ester (IMTSL) and S-4-(4-(dimethylamino)-2-ethyl-5,5-dimethyl-1-oxyl-2,5-dihydro-1H-imidazol-2-yl) benzylmethanethiosulfonate (IKMTSL), with intrinsic pKa’s differing by approximately 2 pH units were used, providing the opportunity to vary the lipid composition in order to investigate effect of the surface charge on dielectric profile at peptide-membrane interface.  Water penetration at the peptide-membrane interface was assessed by hyperfine sublevel correlation spectroscopy (HYSCORE) experiment in which the hyperfine coupling between the nitroxide label and hydrogen/deuterium atom of water is measured.  Supported by NSF-0843632 to TIS.