Lipid nanodiscs solubilized through poly(acrylic acid-co-styrene) copolymers

Copolymers of styrene and acrylic acid form stable nanodiscs that overcome the limitations of styrene maleic acid copolymers, enhancing membrane protein solubilization and purification efficiency for structural biology studies.

AU2020298299B2Pending Publication Date: 2026-07-09THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV +2
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Patent Information

Authority / Receiving Office
AU · AU
Patent Type
Applications
Current Assignee / Owner
THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV
Filing Date
2020-06-19
Publication Date
2026-07-09

AI Technical Summary

Technical Problem

Existing methods for forming native lipid nanodiscs for studying membrane proteins are limited by sensitivity to divalent cations, a narrow pH range, and poor affinity for affinity-based purification methods, with styrene maleic acid copolymers being hydrolyzed and having a limited monomer sequence distribution.

Method used

The use of copolymers composed of styrene and acrylic acid or its derivatives, which form nanodisc assemblies that stabilize lipid bilayers, allowing for the solubilization of membrane proteins and hydrophobic constituents in aqueous solutions, with improved monomer sequence control and regularity.

Benefits of technology

The new copolymers effectively solubilize membrane proteins up to 10-fold more efficiently than conventional styrene maleic acid copolymers, enabling consistent and high-yield extraction for structural studies like cryo-EM, while being compatible with affinity chromatography.

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Abstract

Provided herein are compositions including lipids and copolymers in the form of a nanodisc assembly. The subject copolymers include monomer units of styrene and monomer units selected from acrylic acid and an acrylic acid derivative. In certain cases, the copolymer is a copolymer of styrene and acrylic acid. Also provided herein, is an aqueous solution comprising the subject composition. Also provided herein, are methods for producing a nanodisc assembly, including incubation of a lipid and a subject copolymer. Further provided herein, are methods for solubilizing a membrane protein in an aqueous solution, wherein the method includes forming a nanodisc assembly of a lipid bilayer having one or more membrane proteins embedded therein, and a subject copolymer. Also provided are methods of solubilizing a hydrophobic constituent in an aqueous solution, including forming a nanodisc assembly of a lipid, a hydrophobic constituent, and a subject copolymer.
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