Hydrophobic Functionalization of Polyacrylic Acid as a Versatile Platform for the Development of Polymer Lipid Nanodisks

Abstract

Polymer nanodisks have shown great potential as membrane mimetics that enable the study of functional membrane protein structural biology and also have a wider application in other fields such as drug delivery. To achieve these research goals, the ability to have a cheap, simple, fully customizable platform for future nanodisks technology applications is paramount. Here, a facile functionalization of polyacrylic acid (PAA) with varying hydrophobic groups that form nanodisks at different sizes is successfully demonstrated. The study shows that the choice of hydrophobic group can have a noticeable effect on the polymer solubilization properties and polymer‐induced perturbation to the encased lipid bilayer. Due to this robust, tunable chemical synthesis method, PAA is an exciting platform for the future optimization of the hydrophobic, hydrophilic, or direct purposed functionalizations for polymer nanodisks.Functionalized polyacrylic acid polymers with varying hydrophobic groups form lipid nanodisks. Alkyl‐PAA polymer nanodisks are size tunable by simply varying the lipid:polymer ratio and macro–nanodisks exhibit magnetic alignment. The facile functionalization enables the investigation of the effect of the hydrophobic group of PAA on the nanodisk formation and lipid bilayer properties.