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

Biophysics and Department of Chemistry, University of Michigan, Ann Arbor, MI 48109-1055, USA.
Progress in Nuclear Magnetic Resonance Spectroscopy (Impact Factor: 7.24). 02/2013; 69:1-22. DOI: 10.1016/j.pnmrs.2013.01.001
Source: PubMed


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► Lipid bicelles have matured to full membership in the club of lipid phases. ► Numerous techniques have elucidated the character traits of bicelles. ► Bicelles are exemplary citizens in the realm of model membranes. ► They contribute particularly in studies of membrane protein structure.

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Available from: Ayyalusamy Ramamoorthy, Jul 21, 2014
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    • "However, membrane protein structure determination is an extremely challenging task due to the lack of stability of the protein outside the native membrane environment. For this reason, development of novel methods to stabilize the native structure of membrane proteins is essential for driving high-resolution structural studies using biophysical techniques such as nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography111213141516171819202122. Bicelles are increasingly used as model membranes for the studies of biomolecules with various biophysical methods, including solid-state NMR, solution NMR, X-ray crystallography, EPR (Electron Paramagnetic Resonance), CD (Circular Dichroism), fluorescence, IR (Infra Red), Raman, UV-Vis spectroscopy, ITC (Isothermal Titration Calorimetry), DSC (Differential Scanning Calorimetry), and microscopy, as their planar domain provides an excellent environment for the study of membrane-associated proteins in transparent fluid solutions, which prevent light scattering111214152324252627. "
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    ABSTRACT: Though the importance of high-resolution structure and dynamics of membrane proteins has been well recognized, optimizing sample conditions to retain the native-like folding and function of membrane proteins for Nuclear Magnetic Resonance (NMR) or X-ray measurements has been a major challenge. While bicelles have been shown to stabilize the function of membrane proteins and are increasingly utilized as model membranes, the loss of their magnetic-alignment at low temperatures makes them unsuitable to study heat-sensitive membrane proteins like cytochrome-P450 and protein-protein complexes. In this study, we report temperature resistant bicelles that can magnetically-align for a broad range of temperatures and demonstrate their advantages in the structural studies of full-length microsomal cytochrome-P450 and cytochrome-b5 by solid-state NMR spectroscopy. Our results reveal that the N-terminal region of rabbit cytochromeP4502B4, that is usually cleaved off to obtain crystal structures, is helical and has a transmembrane orientation with ~17° tilt from the lipid bilayer normal.
    Full-text · Article · Aug 2013 · Scientific Reports
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    ABSTRACT: There is significant interest in solving high-resolution dynamic structures of membrane-associated peptides using solid-state NMR spectroscopy. Previous solid-state NMR studies have provided valuable insights into the functional properties of an exciting class of biomacromolecules such as antimicrobial peptides and amyloid peptides. However, it has been a major challenge to apply solid-state NMR techniques to study peptides or proteins that are not labeled with specific isotopes such as 13C, 15N and/or 2H. This study utilizes 2D 1H/1H RFDR (radio-frequency-driven dipolar recoupling) and NOESY pulse sequences under magic angle spinning to study a membrane-bound antimicrobial peptide MSI-78 (or also known as pexiganan). We demonstrate that proton resonances can be assigned and structural constraints - NOE and 1H-1H dipolar couplings - can be measured without the need for any isotopic enrichment. The buildup curves, showing the dependence of the cross peak intensity against the mixing time, obtained from 2D 1H/1H NOESY and RFDR experiments are compared. Our results reveal that the RFDR-recovered 1H-1H dipolar couplings associated with alpha and side chain protons are larger than that with the amide-protons. This study provides a means to measure residual 1H-1H dipolar couplings for the investigation of structure, dynamics, and aggregation of peptides using a suitable model membrane like micelles or bicelles.
    No preview · Article · May 2013 · The Journal of Physical Chemistry B
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    ABSTRACT: In recent years, multi-lipid bicellar systems have emerged as promising membrane models. The fast orientational diffusion and magnetic alignability made these systems very attractive for NMR investigations. However, their alignment was so far achieved with a strong magnetic field, which limited their use with other methods that require macroscopic orientation. Recently, it was shown that bicelles could be aligned also by shear flow in a Couette flow cell, making it applicable to structural and biophysical studies by polarized light spectroscopy. Considering the sensitivity of this lipid system to small variations in composition and physicochemical parameters, efficient use of such a flow-cell method with coupled techniques will critically depend on the detailed understanding of how the lipid systems behave under flow conditions. In the present study we have characterized the flow alignment behavior of the commonly used dimyristoyl phosphatidylcholine/dicaproyl phosphatidylcholine (DMPC/DHPC) bicelle system, for various temperatures, lipid compositions, and lipid concentrations. We conclude that at optimal flow conditions the selected bicellar systems can produce the most efficient flow alignment out of any lipid systems used so far. The highest degree of orientation of DMPC/DHPC samples is noticed in a narrow temperature interval, at a practical temperature around 25°C, most likely in the phase transition region characterized by maximum sample viscosity. The change of macroscopic orientation factor as function of the above conditions is now described in detail. The increase in macroscopic alignment observed for bicelles will most likely allow recording of higher resolution spectra on membrane systems, which provide deeper structural insight and analysis into properties of biomolecules interacting with solution phase lipid membranes.
    No preview · Article · Aug 2013 · Chemistry and Physics of Lipids
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