Dataset Information

A Diazirine-Modified Membrane Lipid to Study Peptide/Lipid Interactions - Chances and Challenges.

ABSTRACT: Although incorporation of photo-activatable lipids into membranes potentially opens up novel avenues for investigating interactions with proteins, the question of whether diazirine-modified lipids are suitable for such studies, remains under debate. Focusing on the potential for studying lipid/peptide interactions by cross-linking mass spectrometry (XL-MS), we developed a diazirine-modified lipid (DiazPC), and examined its behaviour in membranes incorporating the model α-helical peptide LAVA20. We observed an unexpected backfolding of the diazirine-containing stearoyl chain of the lipid. This surprising behaviour challenges the potential application of DiazPC for future XL-MS studies of peptide and protein/lipid interactions. The observations made for DiazPC most likely represent a general phenomenon for any type of membrane lipids with a polar moiety incorporated into the alkyl chain. Our finding is therefore of importance for future protein/lipid interaction studies relying on modified lipid probes.

SUBMITTER: Dorner J

PROVIDER: S-EPMC8597076 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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A Diazirine-Modified Membrane Lipid to Study Peptide/Lipid Interactions - Chances and Challenges.

Dorner Julia J Korn Patricia P Gruhle Kai K Ramsbeck Daniel D Garamus Vasil M VM Lilie Hauke H Meister Annette A Schwieger Christian C Ihling Christian C Sinz Andrea A Drescher Simon S

Chemistry (Weinheim an der Bergstrasse, Germany) 20210928 59

Although incorporation of photo-activatable lipids into membranes potentially opens up novel avenues for investigating interactions with proteins, the question of whether diazirine-modified lipids are suitable for such studies, remains under debate. Focusing on the potential for studying lipid/peptide interactions by cross-linking mass spectrometry (XL-MS), we developed a diazirine-modified lipid (DiazPC), and examined its behaviour in membranes incorporating the model α-helical peptide LAVA20. ...[more]

PMID: 34406694

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Project description:Natural or synthetic polycations are used as biocides or as drug/gene carriers. Understanding the interactions between these macromolecules and cell membranes at the molecular level is therefore of great importance for the design of effective polymer biocides or biocompatible polycation-based delivery systems. Until now, details of the processes at the interface between polycations and biological systems have not been fully recognized. In this study, we consider the effect of strong polycations with quaternary ammonium groups on the properties of anionic lipid membranes that we use as a model system for protein-free cell membranes. For this purpose, we employed experimental measurements and atomic-scale molecular dynamics (MD) simulations. MD simulations reveal that the polycations are strongly hydrated in the aqueous phase and do not lose the water shell after adsorption at the bilayer surface. As a result of strong hydration, the polymer chains reside at the phospholipid headgroup and do not penetrate to the acyl chain region. The polycation adsorption involves the formation of anionic lipid-rich domains, and the density of anionic lipids in these domains depends on the length of the polycation chain. We observed the accumulation of anionic lipids only in the leaflet interacting with the polymer, which leads to the formation of compositionally asymmetric domains. Asymmetric adsorption of the polycation on only one leaflet of the anionic membrane strongly affects the membrane properties in the polycation-membrane contact areas: (i) anionic lipid accumulates in the region near the adsorbed polymer, (ii) acyl chain ordering and lipid packing are reduced, which results in a decrease in the thickness of the bilayer, and (iii) polycation-anionic membrane interactions are strongly influenced by the presence and concentration of salt. Our results provide an atomic-scale description of the interactions of polycations with anionic lipid bilayers and are fully supported by the experimental data. The outcomes are important for understanding the correlation of the structure of polycations with their activity on biomembranes.

Dataset Information

A Diazirine-Modified Membrane Lipid to Study Peptide/Lipid Interactions - Chances and Challenges.

Publications

A Diazirine-Modified Membrane Lipid to Study Peptide/Lipid Interactions - Chances and Challenges.

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