Bicelles and nanodiscs for biophysical chemistry.

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.