On/off switching of lipid bicelle adsorption on titanium oxide controlled by sub-monolayer molecular surface functionalization

Modifying inorganic surfaces with covalently attached organic molecules can be useful to fabricate biomimetic lipid membrane coatings on otherwise intractable surfaces for various applications such as medical implants and biosensors. A classic example is the formation of a hydrophobic, self-assembled monolayer, and a full-spanning monolayer of organic molecules has long been considered a design prerequisite to drive subsequent lipid self-assembly processes in such cases. Expanding on this viewpoint, herein, we demonstrate that functionalizing a titanium oxide (TiO₂) surface with a low surface coverage of hydroxyl-terminated, 11-hydroxyundecylphosphonic acid (HUPA) in the sub-monolayer regime can readily transform the TiO₂ surface in an “on/off” manner from fully repelling zwitterionic lipid bicelle adsorption to supporting formation of a well-packed bicelle adlayer coating that is useful for biosensing applications. Using the quartz crystal microbalance-dissipation (QCM-D) technique, we characterized HUPA deposition in various solvent systems and identified optimal room-temperature, solution-phase deposition conditions while further developing bicelle coating protocols and surface passivation strategies to facilitate selective detection of membrane-protein and antibody-antigen interactions. Strikingly, when chemisorbed HUPA covered <20% of the TiO₂ surface, there was a >25-fold increase in bicelle adsorption compared to the bare TiO₂ case. To rationalize these findings, we discuss mechanistic aspects related to how HUPA attachment dampens steric-hydration forces on the TiO₂ surface and our low-coverage surface functionalization approach in the sub-monolayer regime demonstrates a broadly applicable interfacial science strategy to modulate biomacromolecular adsorption processes and can be useful for bicelle-based, membrane-on-a-chip applications.