Nanodiscs

Nanodiscs are self-assembled discoidal fragments of phospholipids bilayers 7-50 nm in diameter (typically, 8-16 nm in diameter), stabilized by either an amphipathic protein or polymer. Obviously, nanodiscs consist of two main components of phospholipids and stabilizing belt, in which, phospholipids can be synthetic phospholipids or native cell membrane phospholipids, and stabilizing belt that closely surround the phospholipids can be membrane scaffold protein (MSP) or synthetic polymers. The aim of nanodiscs is to simulate the native phospholipid bilayer of cells for target molecules (usually membrane protein) with the strength of providing control over size, composition, and specific functional modifications on the nanometer scale, thus providing a valuable research platform for the solubilization, isolation, purification, and biophysical and biochemical studies of membrane proteins. Since the introduction of this technique, the research of membrane protein has been developed by leaps and bounds.

Fig.1 General structure of nanodisc containing membrane protein.

Types of Nanodiscs

Usually, based on the type of stabilizing belt, the nanodiscs are divided into two main categories of synthetic nanodiscs and MSP nanodiscs.

• Synthetic Nanodiscs: Synthetic nanodiscs are composed of native cell membrane phospholipids and synthetic polymers. Synthetic polymers are the core of this nanodiscs. Styrene-maleic acid (SMA) copolymers, which are formed from polymerized hydrophobic styrene and hydrophilic maleic anhydride monomers, were the first polymers used to for this process. Subsequently, to overcome the limitations of SMA of sensitivity to low pH and divalent cations and absorption of UV light, many novel polymers were developed, including SMA-ED, SMA-EA, SMAd-A, SMA-QA and SMI (these polymers were obtained by functionalisation of the maleic anhydride moiety of SMA), diisobutylene maleic acid (DIBMA), polymethacrylate polymer (PMA), poly(acrylic acid-co-styrene) copolymer (AASTY), etc. Synthetic nanodiscs are most prominent MSP nanodiscs alternative. They offer a unique strategy that allows the membrane proteins to be separated directly from the cell membrane, negating the need for initial detergent solubilization, and retaining the native lipid environment, simultaneously.
• MSP Nanodiscs: MSP nanodiscs are composed of MSP and artificial phospholipid bilayer. MSP plays an important role in the MSP nanodiscs, determining the size of the nanodiscs and making the nanodiscs highly soluble in water. MSP was designed based on apolipoprotein A1 whose globular region was removed, creating a single α-helical segment that is separated by proline residues. The first MSP was known as MSP1 and further modification of MSP1 created many MSP variations with diverse sizes and styles. The more commonly used and representative constructs of MSP in MSP nanodiscs include MSP1D1, MSP1E3D1, MSP2N2, etc. ^[1] The most popular artificial lipids in MSP nanodiscs include phosphatidylcholine (PC), as well as mixtures of PC with charged phospholipids^[2]. MSP nanodiscs have been found to better mimic the natural lipid environment of membrane proteins than detergent micelles, and significantly increase MP stability compared to detergents.

Fig. 2. Structure of (A) MSP nanodiscs and (B) synthetic nanodiscs.

Application of Nanodiscs in Membrane Proteins

The primary application of nanodiscs is to determine the structure of membrane proteins by using techniques such as X-ray crystallography, cryo- and negative staining electron microscopy, nuclear magnetic resonance spectroscopy, spectroscopic methods, etc. Because nanodiscs provide a native-like environment that can maintain the integrity of the membrane proteins, which guarantees the basic requirement of membrane protein structure study, and also provide a small, uniform size that is compatible with many structural techniques. Moreover, nanodiscs are increasingly being used to study the function of membrane proteins and to study the interactions of membrane proteins with other proteins or small molecules. More recently, nanodiscs are also used to study the interactions between membrane proteins and potential drug candidates, aiding in drug discovery and development processes.

Our Nanodiscs Products

Over the years, Alfa Chemistry has been working on the research of nanodiscs and membrane proteins. At present, we have developed a wide range of MSP nanodiscs and synthetic nanodiscs related products, including MSP, SMA, DIBMA, AASTY and other stabilizing belt of nanodiscs, pre-assembled MSP nanodiscs and some kits. Please click the links below for details.

Synthetic Nanodisc Products

SMADIBMAAASTYScreening Kits

MSP Nanodisc Products

Membrane Scaffold Protein (MSP)Pre-assembled NanodiscsNanodisc Assembly Kits

References

1. Pettersen J. M., et al. Advances in nanodisc platforms for membrane protein purification[J]. Trends in Biotechnology, 2023.
2. Denisov I G. and Sligar S. G. Nanodiscs in membrane biochemistry and biophysics[J]. Chemical Reviews, 2017, 117(6): 4669-4713.

Our products and services are for research use only.