A nanodisc is a synthetic model membrane system which assists in the study of

membrane proteins Membrane proteins are common proteins that are part of, or interact with, biological membranes. Membrane proteins fall into several broad categories depending on their location. Integral membrane proteins are a permanent part of a cell membrane ...

. Nanodiscs are discoidal proteins in which a lipid bilayer is surrounded by molecules that are amphipathic molecules including proteins, peptides, and synthetic polymers. It is composed of a

lipid bilayer The lipid bilayer (or phospholipid bilayer) is a thin polar membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around all cells. The cell membranes of almost all organisms and many vir ...

phospholipids Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...

with the hydrophobic edge screened by two

amphipathic An amphiphile (from the Greek αμφις amphis, both, and φιλíα philia, love, friendship), or amphipath, is a chemical compound possessing both hydrophilic (''water-loving'', polar) and lipophilic (''fat-loving'') properties. Such a compoun ...

proteins. These proteins are called membrane scaffolding proteins (MSP) and align in double belt formation. Nanodiscs are structurally very similar to discoidal

high-density lipoprotein High-density lipoprotein (HDL) is one of the five major groups of lipoproteins. Lipoproteins are complex particles composed of multiple proteins which transport all fat molecules (lipids) around the body within the water outside cells. They are ty ...

s (HDL) and the MSPs are modified versions of

apolipoprotein A1 Apolipoprotein AI (ApoA-I) is a protein that in humans is encoded by the ''APOA1'' gene. As the major component of HDL particles, it has a specific role in lipid metabolism. Structure ''APOA1'' is located on chromosome 11, with its specific loca ...

(apoA1), the main constituent in HDL. Nanodiscs are useful in the study of

because they can solubilise and stabilise membrane proteins and represent a more native environment than

liposomes A liposome is a small artificial Vesicle (biology and chemistry), vesicle, spherical in shape, having at least one lipid bilayer. Due to their hydrophobicity and/or hydrophilicity, biocompatibility, particle size and many other properties, lipo ...

, detergent

micelles A micelle () or micella () (plural micelles or micellae, respectively) is an aggregate (or supramolecular assembly) of surfactant amphipathic lipid molecules dispersed in a liquid, forming a colloid, colloidal suspension (also known as associat ...

, bicelles and

amphipols Amphipols (a portmanteau of amphiphilic polymers) are a class of amphiphilic polymers designed to keep membrane proteins soluble in water without the need for detergents, which are traditionally used to this end but tend to be denaturing. Amphipol ...

. The art of making nanodiscs has progressed past using only the MSPs and lipids to make particles, leading to alternative strategies like peptide nanodiscs that use simpler proteins and synthetic nanodiscs that do not need any proteins for stabilization.

MSP nanodisc

The original nanodisc was produced by apoA1-derived MSPs from 2002. The size and stability of these discs depend on the size of these proteins, which can be adjusted by truncation and fusion. In general, MSP1 proteins consist of one repeat, and MSP2s are double-sized.

Peptide nanodisc

In peptide nanodiscs, the lipid bilayer is screened by

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A ...

s instead of two MSPs. Peptide nanodiscs are structurally similar to MSP nanodiscs and the peptides also align in a double belt. They can stabilise membrane proteins, but have higher

polydispersity In chemistry, the dispersity is a measure of the heterogeneity of sizes of molecules or particles in a mixture. A collection of objects is called uniform if the objects have the same size, shape, or mass. A sample of objects that have an incons ...

and are structurally less stable than MSP nanodiscs. Recent studies, however, showed that dimerization and polymerization of the peptides make them more stable.

Synthetic/Native nanodisc

Another way to mimic the native lipid membrane are

synthetic polymers Some familiar household synthetic polymers include: Nylons in textiles and fabrics, Teflon in non-stick pans, Bakelite for electrical switches, polyvinyl chloride (PVC) in pipes, etc. The common PET bottles are made of a synthetic polymer, polye ...

. Styrene-maleic acid co-polymers (SMAs) called SMALPs or Lipodisq and Diisobutylene-maleic acid (DIBMA) are such synthetic polymers (DIBMALPs). They can solubilize membrane proteins directly from

cells Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...

or raw extract. They also have been used to study the lipid composition of several organisms. It was discovered that all synthetic polymers which contained a styrene and maleic acid group can solubilize proteins. These SMA nanoparticles have also been tested as possible drug delivery vehicle and for the study of folding, post-translational modifications and lipid interactions of membrane proteins by native mass spectrometry.

References

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External links

Nanodisc Technology
from the Stephen Sligar laboratory
Assembled nanodiscs
for application with cell-free lysates
HDL and Nanodiscs
an overview of nanodisc technology at UIUC

A summary from the Atkins lab at the University of Washington
Purchase the MSP
The plasmid for the MSP is available from AddGene
SMA native nanodiscs website
International research community website using SMA or other polymers (DIBMA for e.g.) as an alternative to conventional detergents and synthetic lipid environment found in MSP-Nanodisc. Membrane biology