This review covers current trends in studies of membrane amphiphiles and membrane proteins using both fast tumbling bicelles and magnetically aligned bicelle media for both solution state and solid state NMR. The fast tumbling bicelles provide a versatile biologically mimetic membrane model, which in many cases is preferable to micelles, both because of the range of lipids and amphiphiles that may be combined and because radius of curvature effects and strain effects common with micelles may be avoided. Drug and small molecule binding and partitioning studies should benefit from their application in fast tumbling bicelles, tailored to mimic specific membranes. A wide range of topology and immersion depth studies have been shown to be effective in fast tumbling bicelles, while residual dipolar couplings add another dimension to structure refinement possibilities, particularly for situations in which the peptide is uniformly labeled with 15N and 13C. Solid state NMR studies of polytopic transmembrane protei...

Current Applications of Bicelles in NMR Studies of Membrane-Associated Amphiphiles and Proteins†,‡

As of mid 2013 a Medline search on "cholesterol" yielded over 200,000 hits, reflecting the prominence of this lipid in numerous aspects of animal cell biology and physiology under conditions of health and disease. Aberrations in cholesterol homeostasis underlie both a number of rare genetic disorders and contribute to common sporadic and complex disorders including heart disease, stroke, type II diabetes, and Alzheimer's disease. The corresponding author of this review and his lab stumbled only recently into the sprawling area of cholesterol research when they discovered that the amyloid precursor protein (APP) binds cholesterol, a topic covered by the Hans Neurath Award lecture at the 2013 Protein Society Meeting. Here, we first provide a brief overview of cholesterol-protein interactions and then offer our perspective on how and why binding of cholesterol to APP and its C99 domain (β-CTF) promotes the amyloidogenic pathway, which is closely related to the etiology of Alzheimer's disease.

/pdf/cholesterol-as-a-co-solvent-and-a-ligand-for-membrane-11aeek4xxc.pdf

Cholesterol as a co-solvent and a ligand for membrane proteins

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

Mixtures of long- and short-chain phospholipids, specifically 14:0 and 6:0 phosphatidylcholines (DMPC and DHPC), have been used successfully in NMR studies as magnetically alignable substrates for membrane-associated proteins. However, recent publications have shown that the phase behavior of these mixtures is much more complex than originally thought. Using polarized light microscopy and small-angle neutron scattering, phase diagrams of DMPC/DHPC mixtures at molar ratios of 2, 3.2, and 5 have been determined. Generally, at temperatures below the main-chain melting transition of DMPC (T(M) = 23 degrees C), an isotropic phase of disk-like micelles is found. At high temperatures (T > 50 degrees C), a lamellar phase consisting of either multilamellar vesicles (MLV) or extended lamellae is formed, which at low lipid concentrations (e.g., MLV) coexists with an excess of water. At intermediate temperatures and lipid concentrations, a chiral nematic phase made up of worm-like micelles was observed.

Comprehensive examination of mesophases formed by DMPC and DHPC mixtures.

http://if-pan.krakow.pl/pjp/pdf/2011/3_643.pdf

Prem R. Adhikari

Papers

A 2H solid-state NMR spectroscopic investigation of biomimetic bicelles containing cholesterol and polyunsaturated phosphatidylcholine.