Bicelles and nanodiscs for biophysical chemistry1

https://doi.org/10.1016/j.bbamem.2020.183478Get rights and content
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Highlights

  • Bicelles are pure synthetic lipidic discoidal particles of 20–50 nm diameter that may orient parallel or perpendicularly to magnetic fields. They are called “molecular goniometers” and mimic small pieces of biomembranes.

  • Bicelles are stable on narrow ranges of composition, temperature and hydration, can embed charged lipids, cholesterol, peptides and membrane proteins and are used as platforms to gain information on protein structure and dynamics by ssNMR.

  • Bicelle remain aligned for several hours/days outside magnetic fields and relax according to nematic or smectic properties

  • Nanodiscs are smaller particles (10–20 nm) that may be built with a wide variety of lipids and apolipoproteins (MSP) making the rim of the disc.

  • The constraints exerted by the MSP proteins forbid any temperature-driven phase transition, providing a membrane liquid-ordered state on large temperature domains.

Abstract

Membrane nanoobjects are very important tools to study biomembrane properties. Two types are described herein: Bicelles and Nanodiscs. Bicelles are obtained by thorough water mixing of long chain and short chain lipids and may take the form of membranous discs of 10–50 nm. Temperature-composition-hydration diagrams have been established for Phosphatidylcholines and show limited domains of existence. Bicelles can be doped with charged lipids, surfactants or with cholesterol and offer a wide variety of membranous platforms for structural biology. Internal dynamics as measured by solid-state NMR is very similar to that of liposomes in their fluid phase. Because of the magnetic susceptibility anisotropy of the lipid chains, discs may be aligned along or perpendicular to the magnetic field. They may serve as weak orienting media to provide distance information in determining the 3D structure of soluble proteins. In different conditions they show strong orienting properties which may be used to study the 3D structure, topology and dynamics of membrane proteins. Lipid Bicelles with biphenyl chains or doped with lanthanides show long lasting remnant orientation after removing the magnetic field due to smectic-like properties. An alternative to pure lipid Bicelles is provided by nanodiscs where the half torus composed by short chain lipids is replaced by proteins. This renders the nano-objects less fragile as they can be used to stabilize membrane protein assemblies to be studied by electron microscopy. Internal dynamics is again similar to liposomes except that the phase transition is abolished, possibly due to lateral constrain imposed by the toroidal proteins limiting the disc size. Advantages and drawbacks of both nanoplatforms are discussed.

Abbreviations

DCPC
1,2-hexanoyl-1-sn-glycero-3-phosphocholine
DHPC
1,2-heptanoyl-1-sn-glycero-3-phosphocholine
DMPC
1,2-myristoyl-1-sn-glycero-3-phosphocholine
DMPG
1,2-dimyristoyl-sn-glycero-3-phospho-(1′-rac-glycerol)
DMPE
1,2-myristoyl-1-sn-glycero-3-phosphoethanolamine
DMPS
1,2-dimyristoyl-sn-glycero-3-phospho-l-serine
DOPC
1,2-dioleoyl-sn-glycero-3-phosphocholine
DPPC
1,2-dipalmitoyl-sn-glycero-3-phosphocholine
MAS
magic-angle sample spinning
MLV
multilamellar vesicle
MSP
membrane scaffold proteins
NMR
nuclear magnetic resonance
TOCSY
Total Correlation Spectroscopy
NOESY
nuclear overhauser effect spectroscopy
NOE
nuclear overhauser effect
PISA Wheel
Image of Membrane Protein Helical Wheels
SLF
separated local field spectroscopy
PISEMA
polarization inversion spin exchange at magic angle
POPC
1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine
SUV
small unilamellar vesicle
TBBPC
1-tetradecanoyl-2-(4-(4-biphenyl)butanoyl)-sn-glycero-3-phosphocholine
DNA
Deoxyribonucleic acid

Keywords

Bicelles
Nanodiscs
NMR
Membrane peptides & proteins
Lipids
Membrane dynamics

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1

A tribute to Prof Michèle Auger, University Laval, Canada