Specific Lipid Studies in Complex Membranes by Solid-State NMR Spectroscopy

Roy A.M. van Beekveld; Maik G.N. Derks; Raj Kumar; Leanna Smid; Thorben Maass; João Medeiros-Silva; Eefjan Breukink; Markus Weingarth

doi:10.1002/chem.202202472

Specific Lipid Studies in Complex Membranes by Solid-State NMR Spectroscopy

Roy A.M. van Beekveld
, Maik G.N. Derks
, Raj Kumar
, Leanna Smid
, Thorben Maass
, João Medeiros-Silva
, Eefjan Breukink
, Markus Weingarth^*

^*Corresponding author for this work

Utrecht University

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Specific interactions with phospholipids are often critical for the function of proteins or drugs, but studying these interactions at high resolution remains difficult, especially in complex membranes that mimic biological conditions. In principle, molecular interactions with phospholipids could be directly probed by solid-state NMR (ssNMR). However, due to the challenge to detect specific lipids in mixed liposomes and limited spectral sensitivity, ssNMR studies of specific lipids in complex membranes are scarce. Here, by using purified biological ¹³C,¹⁵N-labeled phospholipids, we show that we can selectively detect traces of specific lipids in complex membranes. In combination with ¹H-detected ssNMR, we show that our approach provides unprecedented high-resolution insights into the mechanisms of drugs that target specific lipids. This broadly applicable approach opens new opportunities for the molecular characterization of specific lipid interactions with proteins or drugs in complex fluid membranes.

Original language	English
Article number	e202202472
Number of pages	8
Journal	Chemistry - A European Journal
Volume	28
Issue number	70
DOIs	https://doi.org/10.1002/chem.202202472
Publication status	Published - 15 Dec 2022

Bibliographical note

Funding Information:
This work was funded by the Dutch Research Council (NWO, grant numbers 723.014.003 & 711.018.001 to MW). Experiments at the 1200 MHz instrument were supported by uNMR‐NL, an NWO‐funded Roadmap NMR facility (no. 184.032.207). The present work was part of the research programme of the Netherlands Centre for One Health ( www.ncoh.nl ).

Funding Information:
This work was funded by the Dutch Research Council (NWO, grant numbers 723.014.003 & 711.018.001 to MW). Experiments at the 1200 MHz instrument were supported by uNMR-NL, an NWO-funded Roadmap NMR facility (no. 184.032.207). The present work was part of the research programme of the Netherlands Centre for One Health (www.ncoh.nl).

Publisher Copyright:
© 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.

Funding

This work was funded by the Dutch Research Council (NWO, grant numbers 723.014.003 & 711.018.001 to MW). Experiments at the 1200 MHz instrument were supported by uNMR‐NL, an NWO‐funded Roadmap NMR facility (no. 184.032.207). The present work was part of the research programme of the Netherlands Centre for One Health ( www.ncoh.nl ).

Keywords

antibiotics
cinnamycin
lipids
membranes
solid state NMR

Access to Document

10.1002/chem.202202472Licence: CC BY

Chemistry A European J - 2022 - Beekveld - Specific Lipid Studies in Complex Membranes by Solid‐State NMR SpectroscopyFinal published version, 1.65 MBLicence: CC BY

Cite this

@article{f5e46234962b47c6a42163221c8956e0,

title = "Specific Lipid Studies in Complex Membranes by Solid-State NMR Spectroscopy",

abstract = "Specific interactions with phospholipids are often critical for the function of proteins or drugs, but studying these interactions at high resolution remains difficult, especially in complex membranes that mimic biological conditions. In principle, molecular interactions with phospholipids could be directly probed by solid-state NMR (ssNMR). However, due to the challenge to detect specific lipids in mixed liposomes and limited spectral sensitivity, ssNMR studies of specific lipids in complex membranes are scarce. Here, by using purified biological 13C,15N-labeled phospholipids, we show that we can selectively detect traces of specific lipids in complex membranes. In combination with 1H-detected ssNMR, we show that our approach provides unprecedented high-resolution insights into the mechanisms of drugs that target specific lipids. This broadly applicable approach opens new opportunities for the molecular characterization of specific lipid interactions with proteins or drugs in complex fluid membranes.",

keywords = "antibiotics, cinnamycin, lipids, membranes, solid state NMR",

author = "\{van Beekveld\}, \{Roy A.M.\} and Derks, \{Maik G.N.\} and Raj Kumar and Leanna Smid and Thorben Maass and Jo{\~a}o Medeiros-Silva and Eefjan Breukink and Markus Weingarth",

note = "Funding Information: This work was funded by the Dutch Research Council (NWO, grant numbers 723.014.003 \& 711.018.001 to MW). Experiments at the 1200 MHz instrument were supported by uNMR‐NL, an NWO‐funded Roadmap NMR facility (no. 184.032.207). The present work was part of the research programme of the Netherlands Centre for One Health ( www.ncoh.nl ). Funding Information: This work was funded by the Dutch Research Council (NWO, grant numbers 723.014.003 \& 711.018.001 to MW). Experiments at the 1200 MHz instrument were supported by uNMR-NL, an NWO-funded Roadmap NMR facility (no. 184.032.207). The present work was part of the research programme of the Netherlands Centre for One Health (www.ncoh.nl). Publisher Copyright: {\textcopyright} 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.",

year = "2022",

month = dec,

day = "15",

doi = "10.1002/chem.202202472",

language = "English",

volume = "28",

journal = "Chemistry - A European Journal",

issn = "0947-6539",

publisher = "John Wiley and Sons Inc.",

number = "70",

}

TY - JOUR

T1 - Specific Lipid Studies in Complex Membranes by Solid-State NMR Spectroscopy

AU - van Beekveld, Roy A.M.

AU - Derks, Maik G.N.

AU - Kumar, Raj

AU - Smid, Leanna

AU - Maass, Thorben

AU - Medeiros-Silva, João

AU - Breukink, Eefjan

AU - Weingarth, Markus

N1 - Funding Information: This work was funded by the Dutch Research Council (NWO, grant numbers 723.014.003 & 711.018.001 to MW). Experiments at the 1200 MHz instrument were supported by uNMR‐NL, an NWO‐funded Roadmap NMR facility (no. 184.032.207). The present work was part of the research programme of the Netherlands Centre for One Health ( www.ncoh.nl ). Funding Information: This work was funded by the Dutch Research Council (NWO, grant numbers 723.014.003 & 711.018.001 to MW). Experiments at the 1200 MHz instrument were supported by uNMR-NL, an NWO-funded Roadmap NMR facility (no. 184.032.207). The present work was part of the research programme of the Netherlands Centre for One Health (www.ncoh.nl). Publisher Copyright: © 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.

PY - 2022/12/15

Y1 - 2022/12/15

N2 - Specific interactions with phospholipids are often critical for the function of proteins or drugs, but studying these interactions at high resolution remains difficult, especially in complex membranes that mimic biological conditions. In principle, molecular interactions with phospholipids could be directly probed by solid-state NMR (ssNMR). However, due to the challenge to detect specific lipids in mixed liposomes and limited spectral sensitivity, ssNMR studies of specific lipids in complex membranes are scarce. Here, by using purified biological 13C,15N-labeled phospholipids, we show that we can selectively detect traces of specific lipids in complex membranes. In combination with 1H-detected ssNMR, we show that our approach provides unprecedented high-resolution insights into the mechanisms of drugs that target specific lipids. This broadly applicable approach opens new opportunities for the molecular characterization of specific lipid interactions with proteins or drugs in complex fluid membranes.

AB - Specific interactions with phospholipids are often critical for the function of proteins or drugs, but studying these interactions at high resolution remains difficult, especially in complex membranes that mimic biological conditions. In principle, molecular interactions with phospholipids could be directly probed by solid-state NMR (ssNMR). However, due to the challenge to detect specific lipids in mixed liposomes and limited spectral sensitivity, ssNMR studies of specific lipids in complex membranes are scarce. Here, by using purified biological 13C,15N-labeled phospholipids, we show that we can selectively detect traces of specific lipids in complex membranes. In combination with 1H-detected ssNMR, we show that our approach provides unprecedented high-resolution insights into the mechanisms of drugs that target specific lipids. This broadly applicable approach opens new opportunities for the molecular characterization of specific lipid interactions with proteins or drugs in complex fluid membranes.

KW - antibiotics

KW - cinnamycin

KW - lipids

KW - membranes

KW - solid state NMR

UR - https://www.scopus.com/pages/publications/85140359001

U2 - 10.1002/chem.202202472

DO - 10.1002/chem.202202472

M3 - Article

AN - SCOPUS:85140359001

SN - 0947-6539

VL - 28

JO - Chemistry - A European Journal

JF - Chemistry - A European Journal

IS - 70

M1 - e202202472

ER -

Specific Lipid Studies in Complex Membranes by Solid-State NMR Spectroscopy

Abstract

Bibliographical note

Funding

Keywords

Access to Document

Other files and links

Fingerprint

Cite this