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Lipid domain formation and non-lamellar structures associated with varied lysylphosphatidylglycerol analogue content in a model Staphylococcal plasma membrane

Rehal, Reg, Barker, Robert D., Lu, Zidong, Bui, Tam T., Demé, Bruno, Hause, Gerd, Wölk, Christian, Harvey, Richard D. (2021) Lipid domain formation and non-lamellar structures associated with varied lysylphosphatidylglycerol analogue content in a model Staphylococcal plasma membrane. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1863 (5). Article Number 183571. ISSN 0005-2736. (doi:10.1016/j.bbamem.2021.183571) (KAR id:87663)

Abstract

Dipalmitoyl-3-aza-dehydroxy-lysylphosphatidylglycerol (DP3adLPG), is a chemically stable synthetic analogue of the bacterial lipid lysylphosphatidylglycerol (LPG), designed as a substitute for the notoriously labile native lipid in biophysical investigations. In Staphylococcus aureus, LPG is known to play a role in resistance to antibiotics by altering membrane charge properties in response to environmental stress, but little is known about how LPG influences other bilayer physicochemical properties or lateral organisation, through the formation of complexes with lipids such as phosphatidylglycerol (PG). In this study we have investigated the different phases formed by biomimetic mixtures of 3adLPG and PG in different thermotropic states, using neutron diffraction and electron microscopy. In a DPPG/DP3adLPG 70:30 mol% mixture, two distinct lamellar phases were observed below the lipid melting transition: Lβ′ 1 and Lβ′ 2 with respective periodicities of 82 and 62 Å. Increasing the proportion of DP3adLPG to mimic the effects of environmental stress led to the disappearance of the Lβ′ 1 phase and the formation of an inverse hexagonal phase. The compositions of these different phases were identified by investigating the thermotropic properties of the two mixtures, and probing their interaction with the antimicrobial peptide magainin 2 F5W. We propose that the observed polymorphism results from the preferential formation of either triplet PG-3adLPG-PG, or paired PG-3adLPG complexes, dependent upon the mixing proportions of the two lipids. The relevance of these findings to the role native LPG in S. aureus, are discussed with respect to their influence on antibiotic resistance and lateral membrane organisation.

Item Type: Article
DOI/Identification number: 10.1016/j.bbamem.2021.183571
Subjects: Q Science > QH Natural history
Divisions: Divisions > Division of Natural Sciences > Physics and Astronomy
Depositing User: Robert Barker
Date Deposited: 19 Apr 2021 00:21 UTC
Last Modified: 14 Nov 2022 23:11 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/87663 (The current URI for this page, for reference purposes)

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