Office of Technology Transfer – University of Michigan

Polymer-Based Lipid Nanodiscs and Macrodiscs

Technology #7420

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Researchers
Ayyalusamy Ramamoorthy, Ph.D.
External Link (rams.biop.lsa.umich.edu)
Managed By
Jeremy Nelson
Patent Protection

Provisional Patent Application Filed 62/589,865

Determination of the structure and function of membrane proteins is a challenge due to the difficulty of extracting them from their native environment while preserving the proteins’ native conformation. Traditional protocols involve extraction using detergents, which leads to issues such as protein inactivation and sample aggregation. Recently, methods have been developed that utilize lipid nanodiscs, which are disc-shaped patches of lipid bilayers surrounded by an amphiphilic belt. Various compounds have been used as the amphiphilic belt, including membrane scaffold proteins, peptides, and polymers, but all suffer from disadvantages including restricted size range, stability, non-tolerance to divalent metal ions and pH, and expensive production costs.

A suite of copolymers for enhanced and tunable chemical stability of lipid nanodiscs

Researchers at the University of Michigan have developed a suite of styrene/maleic acid (SMA) based copolymers that address many of these challenges. Although SMA copolymers are a known motif for use in creating lipid nanodiscs, the UM researchers derivatized the maleic acid in order to impart greater stability to the lipid nanodiscs in the presence of divalent metal ions and over wider pH ranges. Selection of the modified SMA copolymer allows for stability over a desired pH range, or over nearly all relevant pHs in the case of one of the copolymers. Synthesis of the copolymers is conducted via chemical derivatization of the already prepared and well-known SMA copolymer.

Applications

* Formation of lipid nanodiscs with greater stability over a defined pH range

* Scientific investigation of membrane-bound proteins in their native conformation

* Potential for use as a drug delivery mechanism

Advantages

* Lipid nanodiscs display greater stability over a defined pH range

* Lipid nanodiscs display greater tolerance to divalent metal ions

* Amphiphilic belt polymers prepared via chemical modification of well-known SMA copolymers