Solubilization of Membrane Proteins Into Functional Lipid-Bilayer Nanodiscs Using a Diisobutylene/Maleic Acid Copolymer

Angew Chem Int Ed Engl. 2017 Feb 6;56(7):1919-1924. doi: 10.1002/anie.201610778. Epub 2017 Jan 12.


Once removed from their natural environment, membrane proteins depend on membrane-mimetic systems to retain their native structures and functions. To this end, lipid-bilayer nanodiscs that are bounded by scaffold proteins or amphiphilic polymers such as styrene/maleic acid (SMA) copolymers have been introduced as alternatives to detergent micelles and liposomes for in vitro membrane-protein research. Herein, we show that an alternating diisobutylene/maleic acid (DIBMA) copolymer shows equal performance to SMA in solubilizing phospholipids, stabilizes an integral membrane enzyme in functional bilayer nanodiscs, and extracts proteins of various sizes directly from cellular membranes. Unlike aromatic SMA, aliphatic DIBMA has only a mild effect on lipid acyl-chain order, does not interfere with optical spectroscopy in the far-UV range, and does not precipitate in the presence of low millimolar concentrations of divalent cations.

Keywords: amphiphilic polymers; biomembranes; membrane mimetics; membrane proteins; protein chromatography.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkenes / chemistry*
  • Detergents / chemistry
  • Escherichia coli / chemistry
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / isolation & purification
  • Lipid Bilayers / chemistry*
  • Liposomes / chemistry
  • Maleates / chemistry*
  • Membrane Proteins / chemistry*
  • Membrane Proteins / isolation & purification
  • Micelles
  • Nanostructures / chemistry
  • Phospholipids / chemistry
  • Polymers / chemistry*
  • Solubility


  • Alkenes
  • Detergents
  • Escherichia coli Proteins
  • Lipid Bilayers
  • Liposomes
  • Maleates
  • Membrane Proteins
  • Micelles
  • Phospholipids
  • Polymers
  • maleic acid
  • diisobutylene