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Influence of Lipid/Peptide Hydrophobic Mismatch on the Thickness of Diacylphosphatidylcholine Bilayers. A 2H NMR and ESR Study Using Designed Transmembrane Alpha-Helical Peptides and Gramicidin A

Influence of Lipid/Peptide Hydrophobic Mismatch on the Thickness of Diacylphosphatidylcholine Bilayers. A 2H NMR and ESR Study Using Designed Transmembrane Alpha-Helical Peptides and Gramicidin A
Influence of Lipid/Peptide Hydrophobic Mismatch on the Thickness of Diacylphosphatidylcholine Bilayers. A 2H NMR and ESR Study Using Designed Transmembrane Alpha-Helical Peptides and Gramicidin A
We have investigated the effect of a series of hydrophobic polypeptides (WALP peptides) on the mean hydrophobic thickness of (chain-perdeuterated) phosphatidylcholines (PCs) with different acyl chain length, using 2H NMR and ESR techniques. The WALP peptides 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, e.g., FmAW2(LA)nW2AEtn. 2H NMR measurements showed that the shortest peptide with a total length of 16 amino acids (WALP16) causes an increase of 0.6 Å in bilayer thickness in di-C12-PC, a smaller increase in di-C14-PC, no effect in di-C16-PC, and a decrease of 0.4 Å in di-C18-PC, which was the largest decrease observed in any of the peptide/lipid systems. The longest peptide, WALP19, in di-C12-PC caused the largest increase in thickness of the series (+1.4 Å), which decreased again for longer lipids toward di-C18-PC, in which no effect was noticed. WALP17 displayed an influence intermediate between that of WALP16 and WALP19. Altogether, incorporation of the WALP peptides was found to result in small but very systematic changes in bilayer thickness and area per lipid molecule, depending on the difference in hydrophobic length between the peptide and the lipid bilayer in the liquid-crystalline phase. ESR measurements with spin-labeled lipid probes confirmed this result. Because thickness is expected to be influenced most at the lipids directly adjacent to the peptides, also the maximal adaptation of these first-shell lipids was estimated. The calculation was based on the assumption that there is little or no aggregation of the WALP peptides, as was supported by ESR, and that lipid exchange is rapid on the 2H NMR time scale. It was found that even the maximal possible changes in first-shell lipid length were relatively small and represented only a partial response to mismatch. The synthetic WALP peptides are structurally related to the gramicidin channel, which was therefore used for comparison. In most lipid systems, gramicidin proved to be a stronger perturber of bilayer thickness than WALP19, although its length should approximate that of the shorter WALP16. The effects of gramicidin and WALP peptides on bilayer thickness were evaluated with respect to previous 31P NMR studies on the effects of these peptides on macroscopic lipid phase behavior. Both approaches indicate that, in addition to the effective hydrophobic length, also the physical nature of the peptide surface is a modulator of lipid order.
9333-9345
de Planque, M R R
a1d33d13-f516-44fb-8d2c-c51d18bc21ba
Greathouse, D V
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Koeppe II, R E
b3a8d97c-f7e2-4cd1-8075-322a28644a1c
Schäfer, H
7ebd03c5-7c26-46a7-942f-7f6d2a3ef156
Marsh, D
099462b8-c3c5-4fc9-982d-1e91d379b3cf
Killian, J A
b54a7210-377f-4cb2-a738-5dcdb953a9bf
de Planque, M R R
a1d33d13-f516-44fb-8d2c-c51d18bc21ba
Greathouse, D V
a1be1f6a-2843-4999-88d7-8de1ece68708
Koeppe II, R E
b3a8d97c-f7e2-4cd1-8075-322a28644a1c
Schäfer, H
7ebd03c5-7c26-46a7-942f-7f6d2a3ef156
Marsh, D
099462b8-c3c5-4fc9-982d-1e91d379b3cf
Killian, J A
b54a7210-377f-4cb2-a738-5dcdb953a9bf

de Planque, M R R, Greathouse, D V, Koeppe II, R E, Schäfer, H, Marsh, D and Killian, J A (1998) Influence of Lipid/Peptide Hydrophobic Mismatch on the Thickness of Diacylphosphatidylcholine Bilayers. A 2H NMR and ESR Study Using Designed Transmembrane Alpha-Helical Peptides and Gramicidin A. Biochemistry, 37 (26), 9333-9345. (doi:10.1021/bj980233r).

Record type: Article

Abstract

We have investigated the effect of a series of hydrophobic polypeptides (WALP peptides) on the mean hydrophobic thickness of (chain-perdeuterated) phosphatidylcholines (PCs) with different acyl chain length, using 2H NMR and ESR techniques. The WALP peptides 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, e.g., FmAW2(LA)nW2AEtn. 2H NMR measurements showed that the shortest peptide with a total length of 16 amino acids (WALP16) causes an increase of 0.6 Å in bilayer thickness in di-C12-PC, a smaller increase in di-C14-PC, no effect in di-C16-PC, and a decrease of 0.4 Å in di-C18-PC, which was the largest decrease observed in any of the peptide/lipid systems. The longest peptide, WALP19, in di-C12-PC caused the largest increase in thickness of the series (+1.4 Å), which decreased again for longer lipids toward di-C18-PC, in which no effect was noticed. WALP17 displayed an influence intermediate between that of WALP16 and WALP19. Altogether, incorporation of the WALP peptides was found to result in small but very systematic changes in bilayer thickness and area per lipid molecule, depending on the difference in hydrophobic length between the peptide and the lipid bilayer in the liquid-crystalline phase. ESR measurements with spin-labeled lipid probes confirmed this result. Because thickness is expected to be influenced most at the lipids directly adjacent to the peptides, also the maximal adaptation of these first-shell lipids was estimated. The calculation was based on the assumption that there is little or no aggregation of the WALP peptides, as was supported by ESR, and that lipid exchange is rapid on the 2H NMR time scale. It was found that even the maximal possible changes in first-shell lipid length were relatively small and represented only a partial response to mismatch. The synthetic WALP peptides are structurally related to the gramicidin channel, which was therefore used for comparison. In most lipid systems, gramicidin proved to be a stronger perturber of bilayer thickness than WALP19, although its length should approximate that of the shorter WALP16. The effects of gramicidin and WALP peptides on bilayer thickness were evaluated with respect to previous 31P NMR studies on the effects of these peptides on macroscopic lipid phase behavior. Both approaches indicate that, in addition to the effective hydrophobic length, also the physical nature of the peptide surface is a modulator of lipid order.

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Published date: April 1998
Organisations: Nanoelectronics and Nanotechnology

Identifiers

Local EPrints ID: 264715
URI: http://eprints.soton.ac.uk/id/eprint/264715
PURE UUID: 2374dddf-9f7a-4f81-a605-b004a303e553
ORCID for M R R de Planque: ORCID iD orcid.org/0000-0002-8787-0513

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Date deposited: 22 Oct 2007
Last modified: 14 Mar 2024 07:55

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Author: M R R de Planque ORCID iD
Author: D V Greathouse
Author: R E Koeppe II
Author: H Schäfer
Author: D Marsh
Author: J A Killian

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