Mechanisms of Formation, Structure, and Dynamics of Lipoprotein Discs Stabilized by Amphiphilic Copolymers: A Comprehensive Review

Abstract

Amphiphilic copolymers consisting of alternating hydrophilic and hydrophobic units account for a major recent methodical breakthrough in the investigations of membrane proteins. Styrene–maleic acid (SMA), diisobutylene–maleic acid (DIBMA), and related copolymers have been shown to extract membrane proteins directly from lipid membranes without the need for classical detergents. Within the particular experimental setup, they form disc-shaped nanoparticles with a narrow size distribution, which serve as a suitable platform for diverse kinds of spectroscopy and other biophysical techniques that require relatively small, homogeneous, water-soluble particles of separate membrane proteins in their native lipid environment. In recent years, copolymer-encased nanolipoparticles have been proven as suitable protein carriers for various structural biology applications, including cryo-electron microscopy (cryo-EM), small-angle scattering, and conventional and single-molecule X-ray diffraction experiments. Here, we review the current understanding of how such nanolipoparticles are formed and organized at the molecular level with an emphasis on their chemical diversity and factors affecting their size and solubilization efficiency.

Alternatives to Styrene‐ and Diisobutylene‐Based Copolymers for Membrane Protein Solubilization via Nanodisc Formation

“…As a note, the particle sizes measured using TEM appear to be smaller than those measured using DLS, an anomaly that has been previously reported. [31] Between all the data presented here, it is clear that C 14 MA samples are solubilizing trimeric PSI into lipid-containing nanodiscs directly from the cellular membrane of Te.…”

Effect of Cholesterol on the Structure and Composition of Glyco-DIBMA Lipid Particles

“…Glyco-DIBMALPs are formed by incubating lipid vesicles with a polymer solution. It has been reported for other amphiphilic co-polymers, such as SMA and DIBMA, that the polymer molecules initially associate with the vesicles and subsequently induce a destabilization of the lipid bilayer, which results in the extraction of lipid bilayer patches that form the lipid core of the nanodisc-like polymer–lipid particles . The packing of the lipids within the vesicle can affect the initial insertion of the polymer units within the hydrophobic region of the bilayer, which is a fundamental step for the formation of the discoidal particles .…”

The effect of polymer end-group on the formation of styrene – maleic acid lipid particles (SMALPs)

“…13,18 While SMA copolymers dominate published studies, the copolymers are effective only over a narrow pH range (7)(8)(9) and are sensitive to small concentrations of divalent cations. Several structural variants 13 of SMA as well as a small number of other copolymers [19][20][21] have been found to produce SMALP-like nanodiscs, although only a few workable copolymer variants have been widely exploited thus far.…”