Polymer Science

Synthesis and Evaluation of a Novel Library of Alternating Amphipathic Copolymers to Solubilize and Study Membrane Proteins

Authors

Abstract

Amphipathic copolymers such as poly(styrene-maleic acid) (SMA) are promising tools for the facile extraction of membrane proteins (MPs) into native nanodiscs. Here, we designed and synthesized a library of well-defined alternating copolymers of SMA analogues in order to elucidate polymer properties that are important for MP solubilization and stability. MP extraction efficiency was determined using KcsA from E.coli membranes and general solubilization efficiency was investigated via turbidimetry experiments on membranes of E.coli, yeast mitochondria and synthetic lipids. Remarkably, halogenation of SMA copolymers dramatically improved solubilization efficiency in all systems, while substituents on the copolymer backbone improved resistance to Ca2+. Relevant polymer properties were found to include hydrophobic balance, size and positioning of substituents, rigidity and electronic effects. The library thus contributes to the rational design of copolymers for the study of MPs.

Content

Thumbnail image of Manuscript SMA Analogues Preprint.pdf

Supplementary material

Thumbnail image of MS SMA Analogues Supporting Information - Preprint.pdf
SI - SMA Analogues
Supporting Information - Synthesis and Evaluation of a Novel Library of Alternating Amphipathic Copolymers to Solubilize and Study Membrane Proteins