The University of Southampton
University of Southampton Institutional Repository

Induction of Nonbilayer Structures in Diacylphosphatidylcholine Model Membranes by Transmembrane Alpha-Helical Peptides: Importance of Hydrophobic Mismatch and Proposed Role of Tryptophans

Killian, J A, Salemink, I, de Planque, M R R, Lindblom, G, Koeppe II, R E and Greathouse, D V (1996) Induction of Nonbilayer Structures in Diacylphosphatidylcholine Model Membranes by Transmembrane Alpha-Helical Peptides: Importance of Hydrophobic Mismatch and Proposed Role of Tryptophans Biochemistry, 35, (3), pp. 1037-1045.

Record type: Article


We have investigated the effect of several hydrophobic polypeptides on the phase behavior of diacylphosphatidylcholines with different acyl chain length. The polypeptides are uncharged and consist of a sequence with variable length of alternating leucine and alanine, flanked on both sides by two tryptophans, and with the N- and C-termini blocked. First it was demonstrated by circular dichroism measurements that these peptides adopt an -helical conformation with a transmembrane orientation in bilayers of dimyristoylphosphatidylcholine. Subsequent 31P NMR measurements showed that the peptides can affect lipid organization depending on the difference in hydrophobic length between the peptide and the lipid bilayer in the liquid-crystalline phase. When a 17 amino acid residue long peptide (WALP17) was incorporated in a 1/10 molar ratio of peptide to lipid, a bilayer was maintained in saturated phospholipids containing acyl chains of 12 and 14 C atoms, an isotropic phase was formed at 16 C atoms, and an inverted hexagonal (HII) phase at 18 and 20 C atoms. For a 19 amino acid residue long peptide (WALP19) similar changes in lipid phase behavior were observed, but at acyl chain lengths of 2 C-atoms longer. Also in several cis-unsaturated phosphatidylcholine model membranes it was found that these peptides and a shorter analog (WALP16) induce the formation of nonbilayer structures as a consequence of hydrophobic mismatch. It is proposed that this unique ability of the peptides to induce nonbilayer structures in phosphatidylcholine model membranes is due to the presence of two tryptophans at both sides of the membrane/water interface, which prevent the peptide from aggregating when the mismatch is increased. Comparison of the hydrophobic length of the bilayers with the length of the different peptides showed that it is the precise extent of mismatch that determines whether the preferred lipid organization is a bilayer, isotropic phase, or HII phase. The peptide-containing bilayer and HII phase were further characterized after sucrose density gradient centrifugation of mixtures of WALP16 and dioleoylphosphatidylcholine. 31P NMR measurements of the isolated fractions showed that a complete separation of both components was obtained. Chemical analysis of these fractions in samples with varying peptide concentration indicated that the HII phase is highly enriched in peptide (peptide/lipid molar ratio of 1/6), while the maximum solubility of the peptide in the lipid bilayer is about 1/24 (peptide/lipid, molar). A molecular model of the peptide-induced HII phase is presented that is consistent with the results obtained thus far.

Full text not available from this repository.

More information

Published date: 1996
Organisations: Nanoelectronics and Nanotechnology


Local EPrints ID: 264720
PURE UUID: 4ba38ad0-8439-4dbd-bd7d-4915268a8551
ORCID for M R R de Planque: ORCID iD

Catalogue record

Date deposited: 22 Oct 2007
Last modified: 09 Oct 2017 02:54

Export record


Author: J A Killian
Author: I Salemink
Author: G Lindblom
Author: R E Koeppe II
Author: D V Greathouse

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton:

ePrints Soton supports OAI 2.0 with a base URL of

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.