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Review
. 2013 Feb:69:1-22.
doi: 10.1016/j.pnmrs.2013.01.001. Epub 2013 Jan 23.

When detergent meets bilayer: birth and coming of age of lipid bicelles

Ulrich H N Dürr  1 , Ronald Soong, Ayyalusamy Ramamoorthy
Affiliations
Review

When detergent meets bilayer: birth and coming of age of lipid bicelles

Ulrich H N Dürr et al. Prog Nucl Magn Reson Spectrosc. 2013 Feb.
No abstract available

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Figures

Fig. 1
Fig. 1
Lipid bicelles are supramolecular aggregates that are formed when appropriate amounts of lipids and detergents are mixed in an aqueous environment. The size and phase of bicellar aggregates depend on the [lipid]:[detergent] ratio as well as on the temperature. Two fundamentally different phases of bicellar preparations have proven highly useful in the study of protein structure using NMR spectroscopy: isotropic bicelles rapidly tumble freely and are formed at a high detergent concentration (A and B). At low detergent concentrations extended bilayered lamellae are formed (C and D), that spontaneously align macroscopically in a magnetic field. Cryo-TEM micrographs (A and C) are reproduced from the literature [1]. Micrograph (A) contains arrows marked A and B that point to disk-like bicelles viewed from the side and the top, respectively.
Fig. 2
Fig. 2
Different types of model membrane samples suitable for studying membrane proteins by NMR spectroscopy: (A) lipid bilayers (inset) are present in multilamellar vesicles; (B) small unilamellar vesicles and macroscopically-aligned bilayer samples using either (C) glass plates or (D) cylindrical nanopores in anodic aluminum oxide. (E) Micelles are formed from pure detergents. When lipid and detergent mix, isotropic bicelles (F) and magnetically-aligned bicelles (G) are formed. Light gray color indicates a lipid bilayer, dark gray is detergent, and hatching represents either a glass plate (C) or aluminum oxide (D) as solid supporting material.
Fig. 3
Fig. 3
The overall geometrical shape of detergents tends to be conical (A), while phospholipid molecules have mostly cylindrical overall geometry (B). The geometry of pegylated phospholipids again tends to be conical (C).
Fig. 4
Fig. 4
(A) In the absence of a magnetic field, bicelles assume random orientations. (B) Anisotropy in magnetic susceptibility causes macroscopic alignment of bicelles when an external magnetic field is applied.
Fig. 5
Fig. 5
In the presence of lanthanide ions (light spheres), lipid bicelles adopt an orientation where the bilayer normal is parallel to the applied magnetic field (A). This is termed as “flipped” bicelle with respect to the perpendicular orientation adopted by undoped bicelles (B).
Fig. 6
Fig. 6
The morphology of bicellar preparations is dependent on the ratio q between a long-chain lipid and a detergent. Fast tumbling bicelles exist when q < 2.5 (left panel), macroscopically aligned bicelles exist between q ratios of 2.5 and 7.5 (middle), and at high q > 7.5, multilamellar vesicles are formed (right).
Fig. 7
Fig. 7
Bicelles exhibit a wide range of morphologies. Beside the simple nanodisk morphology, multilamellar vesicles (A), chiral nematic ribbons (B), and perforated lamellae (C) are found under different sample conditions.
Fig. 8
Fig. 8
In a lipid bilayer system, only two components are needed to describe the diffusion tensor. The relative orientation of the bilayer normal and hence the principal components of the diffusion with respect to the external magnetic field is described by the angle θ. It determines the component Dzzlab of the diffusion tensor that lines up with the magnetic field and can be measured.
Fig. 9
Fig. 9
STE-PFG NMR pulse sequence composed of three 90° radio frequency pulses and two gradient pulses of identical amplitude and duration. The STE-PFG NMR experiment is arranged such that the decay of the echo intensity, as a function of δ, g or Δ, is proportional to the diffusion coefficient of the species of interest.
Fig. 10
Fig. 10
13C NMR spectroscopy of magnetically-aligned DMPC/DHPC bicelles, q = 3.5. At this ratio of long- to short-chain component, resonances from the long-chain component dominate the spectra. (A) Molecular structure of DMPC, including the commonly employed nomenclature. (B) The natural-abundance 13C NMR chemical shift spectrum on a 400 MHz NMR spectrometer shows clearly resolved resonances for most carbon sites in DMPC. (C) A 400 MHz 2D SLF-spectrum correlates 13C chemical shift to 1H–13C dipolar coupling of carbon nuclei to adjacent hydrogen nuclei and yields information on the local structure and mobility of lipid molecules in bicelles.
Fig. 11
Fig. 11
Order parameter profiles determined from 2D 1H–13C-PELF NMR spectra of magnetically-aligned DMPC/DHPC bicelles [193]. (A) DMPC structure with nomenclature and indication of distinct molecular regions. Order parameter profiles were determined for different values of (B) composition q, (C) temperature and (D) hydration level. These results demonstrate that experimentally measured 13C–1H dipolar couplings can be utilized in measuring the changes in the order/disorder associated with various regions of the lipid and detergent in bicelles without the need for isotopic enrichment. Such measurements have been shown to provide insights into the mechanism of membrane disruption by antimicrobial peptides and amyloid peptides/proteins.
Fig. 12
Fig. 12
Graphic representation of the four fundamentally different ways in which bicelles are used in protein structure and protein–membrane interaction studies. Integral membrane proteins can be studied in aligned (A) as well as isotropically tumbling bicelles (B). Aligned bicelles can be used to impose a residual orientation on soluble proteins for RDC measurements (C). Isotropic as well as aligned bicelles can be used to study membrane interaction of soluble proteins (D).
See this image and copyright information in PMC

References

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