Polymer nanodiscs: Advantages and limitations

There is considerable interest in the development of membrane mimetics to study the structure, dynamics and function of membrane proteins. Polymer nanodiscs have been useful as a membrane mimetic by not only providing a native-like membrane environment, but also have the ability to extract the desired membrane protein directly from the cell membrane. In spite of such great potential, polymer nanodiscs have their disadvantages including lack of size control and instability at low pH and with divalent metals. In this review, we discuss how these limitations have been overcome by simple modifications of synthetic polymers commonly used to form nanodiscs. Recently, size control has been achieved using an ethanolamine functionalization of a low molecular weight polymer. This size control enabled the use of polymer-based lipid-nanodiscs in solution NMR and macronanodiscs in solid-state NMR applications. The introduction of quaternary ammonium functional groups has been shown to improve the stability in the presence of low pH and divalent metal ions, forming highly mono dispersed nanodiscs. The polymer charge has been shown to play a significant role on the reconstitution of membrane proteins due to the high charge density on the nanodisc's belt. These recent developments have expanded the applications of polymer nanodiscs to study the membrane proteins using wide variety of techniques including NMR, Cryo-EM and other biophysical techniques.