Altering the edge chemistry of bicelles with peptoids

Cell function is tied to the interactions that occur within and across the cell membrane. Therefore, understanding membrane-affiliated interactions is important to many biomedical applications. Advancing the body of knowledge about these interactions will lead to discoveries in biomarker detection and therapeutic targets for disease detection and treatment. Model membrane systems are an effective way to study membrane proteins for such discoveries, allowing for stable protein structure and maintaining native activity. Bicelles, disc-shaped lipid bilayers created by combining long- and short-chain phospholipids, are the model membrane system of focus in this study. Bicelles are accessible from both sides and have a wide size range, which makes them attractive for studying membrane interactions without affecting function. In this work, bicelles were functionalized with peptoids to alter the edge chemistry. Peptoids are suitable for this application because of the large diversity of available side chain chemistries that can be easily incorporated in a sequence-specific manner. The peptoid sequence consists of three functional regions to promote insertion into the edge of bicelles. The insertion sequence at the C-terminus contains two alkyl chains and two hydrophobic, chiral aromatic groups that anchor into the bicelle edge. The facially amphipathic helix contains chiral aromatic groups on one side that interact with the lipid tails and positively charged groups on the other side, which interact with the lipid head groups. Thiol groups are included at the N-terminus to allow for visualization of peptoid location in the bicelle. Bicelle morphology and size were assessed by transmission electron microscopy (TEM) and dynamic light scattering (DLS). Peptoid location in the bicelle was determined by attachment of gold nanoparticles, which confirmed preferential incorporation of the peptoid into the bicelle edge with 82% specificity. Additionally, the peptoid-functionalized bicelles are of similar size and morphology to non-functionalized bicelles. Results from this study show that peptoid-functionalized bicelles are a promising model membrane system with potential applications in biosensors or bioseparations.