Polymer nanodiscs: Advantages and limitations

Abstract

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 macro-nanodiscs 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 monodispersed 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.

Materials for Immunotherapy

“…These nanodiscs served as drug carriers to induce immunogenic cancer cell death, thus sensitizing tumors to an immune checkpoint blockade when combined with anti‐PD‐1 therapy. While nanodiscs merit continued investigation, certain limitations must be addressed, including poor stability, limited size control, and finite loading capacities, as discussed elsewhere …”

“…While nanodiscs merit continued investigation, certain limitations must be addressed, including poor stability, limited size control, and finite loading capacities, as discussed elsewhere. [253]…”

Nanodiscs: A toolkit for membrane protein science

“…Indeed, even α‐synuclein 50 and apo‐myoglobin, with its five helices, can solubilize lipids into 10‐nm structures 51 . The use of amphipathic polymers, first those of styrene maleic acid pioneered by Dafforn and co‐workers, 52 and extended to other block copolymers of defined charge and hydrophobicity 53–55 are also finding increasing use. An extensive comparison of these various means for rendering membrane proteins suitable for biophysical structure determination is beyond the scope of this article.…”

The hydrodynamic motion of Nanodiscs

“…SMALPs and other peptide-based methods are described in several articles in this special issue. Although a full review of these kinds of nanodiscs is beyond the scope of this manuscript, various peptide and polymer-based nanodiscs have also been described for solubilizing membranes and reconstituting membrane proteins [9][10][11][12][13] and are discussed in further detail elsewhere in this special issue.…”