Rupture of Stochastically Occurring Vesicle Clusters Limits Bilayer Formation on Alkane–PEG-Type Supports: Uncoupling Clustering from Surface Coverage

Polymer-supported bilayers (PSBs) are a recognized tool for drug discovery through function-interaction analysis of membrane proteins. While silica-supported bilayers (SSBs) spontaneously form from surface-adsorbed vesicles, successful PSB formation via a similar method has thus far been limited by an insufficient understanding of the underlying vesicle-remodelling processes. Here, we generated a polymer support through the incubation of poly-l-lysine conjugated to alkyl-chain-terminated poly(ethylene)glycol on silica. This polymer-coated silica substrate yielded efficient vesicle adsorption and spontaneous bilayer formation, thereby providing a rare opportunity to address the mechanism of PSB formation and compare it to that of SSB. The combined use of super-resolution imaging, kinetics, and simulations indicates that the rupture of stochastically formed vesicle clusters is the rate-limiting step, which is an order of magnitude higher for silica than for polymer-coated silica. This was confirmed by direc...