Membrane thinning due to antimicrobial peptide binding - An atomic force microscopy study of MSI-78 in lipid bilayers

¹ University of Michigan
² The University of Michigan

^* To whom correspondence should be addressed. E-mail: mbanasza{at}umich.edu.

Submitted on March 9, 2005
Revised on April 14, 2005
Accepted on 7 September 2005

	Abstract

The interaction of an antimicrobial peptide, MSI-78, with phospholipid bilayers has been investigated using atomic force microscopy (AFM), circular dichroism (CD) and nuclear magnetic resonance (NMR). Binding of amphipathic peptide helices with their helical axis parallel to the membrane surface leads to membrane thinning. AFM of supported 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayers in the presence of MSI-78 provides images of the membrane thinning process at a high spatial resolution. This data reveals that the membrane thickness is not reduced uniformly over the entire bilayer area. Instead, peptide binding leads to the formation of distinct domains where the bilayer thickness is reduced by 1.1¡Ó0.2 nm. The data is interpreted using a previously published geometric model for the structure of the peptide-lipid domains. In this model the peptides reside at the hydrophilic-hydrophobic boundary in the lipid head group region which leads to an increased distance between lipid head groups. This picture is consistent with concentration dependent ³¹P and ²H NMR spectra of MSI-78 in mechanically aligned DMPC bilayers. Furthermore, ²H NMR experiments on DMPC-d₅₄ multilamellar vesicles indicate that the acyl chains of DMPC are highly disordered in the presence of the peptide as is to be expected for the proposed structure of the peptide-lipid assembly.

Key Words: AFM, Antimicrobial peptide, NMR, lipid bilayer, membrane thinning

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