Bilayer interactions of pHLIP, a peptide that can deliver drugs and target tumors

Biophys J. 2008 Jul;95(1):225-35. doi: 10.1529/biophysj.107.124156. Epub 2008 Mar 21.

Abstract

The pH-dependent insertion of pHLIP across membranes is proving to be a useful property for targeting acidic tissues or tumors and delivering drugs attached to its C-terminus. It also serves as a model peptide for studies of protein insertion into membranes, so further elucidation of the insertion mechanism of pHLIP and its features is desirable. We examine how the peptide perturbs a model phosphatidylcholine membrane and how it associates with the lipid bilayer using an array of fluorescence techniques, including fluorescence anisotropy measurements of TMA-DPH anchored in bilayers, quenching of pHLIP fluorescence by brominated lipids and acrylamide, and measurements of energy transfer between aromatic residues of pHLIP and TMA-DPH. When pHLIP is bound to the surface of bilayers near neutral pH, the membrane integrity is preserved whereas the elastic properties of bilayers are changed as reported by an increase of membrane viscosity. When it is inserted, there is little perturbation of the lipids. The results also suggest that pHLIP can bind to the membrane surface in a shallow or a deep mode depending on the phase state of the lipids. Using parallax analysis, the change of the penetration depth of pHLIP was estimated to be 0.4 A from the bilayer center and 2.8 A from the membrane surface after the liquid-to-gel phase transition.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Computer Simulation
  • Diffusion
  • Drug Carriers / chemistry*
  • Humans
  • Hydrogen-Ion Concentration
  • Lipid Bilayers / chemistry*
  • Membrane Fluidity*
  • Models, Chemical*
  • Models, Molecular*
  • Neoplasms / drug therapy
  • Peptides / chemistry*
  • Phase Transition
  • Viscosity

Substances

  • Drug Carriers
  • Lipid Bilayers
  • Peptides