Self ‐Assembly of Protein‐Containing Lipid‐Bilayer Nanodiscs from Small‐Molecule Amphiphiles

Two small-molecule amphiphiles with diglucose headgroups and either a hydrocarbon or a fluorocarbon hydrophobic chain directly assemble lipids and membrane proteins to form lipid-bilayer nanodiscs. These self-assembled nanostructures have a gentle effect on the encapsulated lipid-bilayer core and membrane proteins. The fluorinated amphiphile appears particularly promising because its chain is both hydrophobic and lipophobic. AbstractWhen membrane proteins are removed from their natural environment, the quality of the membrane-solubilizing agent used is critical for preserving their native structures and functions. Nanodiscs that retain a lipid-bilayer core around membrane proteins have attracted great attention because they offer a much more native-like environment than detergent micelles. Here, two small-molecule amphiphiles with diglucose headgroups and either a hydrocarbon or a fluorocarbon hydrophobic chain are shown to directly assemble lipids and membrane proteins to form native nanodiscs rather than mixed micelles. Self-assembly of nanodiscs of increasing complexity from both defined, artificial vesicles as well as complex, cellular membranes is demonstrated. A detailed investigation of bilayer integrity and membrane-protein activity in these nanodiscs reveals gentle effects on the encapsulated bilayer core. The fluorinated amphiphile appears particularly promising because its lipophobicity results in gentle, non-perturbing interactions with the nanoscale lipid bilayer...

Source: Small - October 21, 2021 Category: Nanotechnology Authors: Florian Mahler, Annette Meister, Carolyn Vargas, Gr égory Durand, Sandro Keller Tags: Research Article Source Type: research