nanodisc

Nanodiscs are nanoscale, discoidal segments of phospholipid bilayer stabilized by belt-like scaffold proteins, designed to solubilize and study membrane proteins in a near-native setting. The most common form uses membrane scaffold proteins derived from apolipoprotein A-I, which wrap around a patch of lipid to form a circular, monodisperse disc.

Structure and preparation: A defined amount of phospholipid and MSPs assemble into discs when detergent is removed, yielding a stable lipid bilayer core surrounded by the MSP belt. Size is controlled by the MSP length: shorter variants (eg, MSP1D1) produce discs around 8–10 nm in diameter, while longer variants give larger discs (up to about 12–15 nm). Lipid composition is flexible, allowing standard phospholipids, cholesterol, and various lipid mixtures to be used.

Variants and scope: While MSP-based nanodiscs are the traditional form, polymer-based nanodiscs extend the concept using amphipathic polymers such as styrene-mul

eic acid (SMA) or diisobutylene maleic anhydride (DIBMA) to solubilize membranes and form SMALPs or related particles. These approaches can encapsulate membrane patches without detergents, enabling studies of native lipid environments and protein-lipid interactions.

Applications: Nanodiscs are used to reconstitute membrane proteins for structural biology (cryo-EM, NMR, X-ray), functional assays, ligand binding studies, and drug screening. They offer a detergent-free, homogeneous, and well-defined platform that preserves native-like lipid surroundings and is compatible with many analytical techniques.

Limitations: Their suitability depends on the protein and lipid requirements; disc size, lipid composition, and potential interactions with scaffold proteins or polymers may affect protein function or data interpretation.