Lipid Nanodiscs via Ordered Copolymers

Amphiphilic copolymers capable of extracting membrane proteins directly from lipid bilayers into “native nanodiscs” promise a simpler membrane protein sample preparation procedure for structural and functional studies. Unfortunately, the selection of nanodisc-forming copolymers is currently limited to molecules that are heterogeneous in terms of molecular weight and monomer sequence, limiting their efficacy in extracting membrane proteins. Here, we report the development of a highly alternating copolymer composed of acrylic acid and styrene by taking advantage of the fundamental reactivity ratios of these monomers. We show that these copolymers, which we term AASTY, are effective solubilizers of membrane proteins expressed in mammalian cells by virtue of their structured amphiphilicity. These AASTY copolymers are promising alternatives to styrene-maleic acid copolymers and provide a new chemical platform for structural and functional characterization of integral membrane proteins in native nanodiscs.