Electrochemical screening of self-assembling β-sheet peptides using supported phospholipid monolayers

Protopapa, E.; Aggeli, A.; Boden, N.; Knowles, P.F.; Salay, L.C.; Nelson, A.

doi:10.1016/j.medengphy.2006.05.002

« Previous Next »Medical Engineering & Physics
Volume 28, Issue 10 , Pages 944-955, December 2006

Electrochemical screening of self-assembling β-sheet peptides using supported phospholipid monolayers

E. Protopapa
- Center for Self Organising Molecular Systems, School of Chemistry, University of Leeds, LS2 9JT, UK
A. Aggeli
- Center for Self Organising Molecular Systems, School of Chemistry, University of Leeds, LS2 9JT, UK
N. Boden
- Center for Self Organising Molecular Systems, School of Chemistry, University of Leeds, LS2 9JT, UK
P.F. Knowles
- School of Biochemistry and Molecular Biology, University of Leeds, LS2 9JT, UK
L.C. Salay
- Center for Self Organising Molecular Systems, School of Chemistry, University of Leeds, LS2 9JT, UK
- Present address: Laboratory of Structural Biology, Department of Biochemistry, Institute of Chemistry, University of Sao Paulo, CP 26077, 05513-970 Sao Paulo, Brazil.
A. Nelson
- Center for Self Organising Molecular Systems, School of Chemistry, University of Leeds, LS2 9JT, UK
- Corresponding author. Tel.: +44 113 6409; fax: +44 113 6452.

Received 28 April 2006; accepted 4 May 2006. published online 28 June 2006.

Abstract

In the context of the medical applications of β-sheet self-assembling peptides, it is important to be able to predict their activity at the biological membrane level. A study of the interaction of four systematically varied 11-residue (P11-1, P11-2, P11-6 and P11-7) and one 13-residue (P13-1) designed β-sheet self-assembling peptides with DOPC monolayers on a mercury electrode is reported in this paper. Experiments were carried out in 0.1moldm⁻³ KCl electrolyte with added phosphate buffer (0.001moldm⁻³) at pH∼7.6. The capacity–potential curves of the coated electrode in the presence and absence of the different peptides were measured using out-of-phase ac voltammetry. The frequency dependence of the complex impedance of the coated electrode surfaces in the presence and absence of the peptides was estimated between 65,000 and 0.1Hz at −0.4V versus Ag/AgCl 3.5mol⁻³dm⁻³ KCl. The monolayer permeabilising properties of the peptides were studied by following the reduction of Tl(I) to Tl(Hg) at the coated electrode. Of the five peptides studied, P11-2, P11-7 and P13-1 interact most strongly with the DOPC layer. P11-1 which has a polar primary structure shows no obvious interaction with the phospholipid but surprisingly, it permeabilises the phospholipid layer to Tl⁺.