Modulating noncovalent and covalent forces to control inverse phosphocholine lipid self-assembly on inorganic surfaces: Nanoarchitectonic design principles

While noncovalent forces typically drive lipid vesicle adsorption and rupture to form supported lipid bilayer (SLB) coatings on inorganic surfaces for various material science applications, this strategy only works on a few materials with suitable energetics such as SiO2. The use of coordination chemistry between inverse phosphocholine (PC) lipid headgroups and surfaces has emerged as a promising strategy to enable SLB formation on other materials such as TiO2 based on covalent forces. However, until now, a cohesive picture of how noncovalent and covalent forces jointly contribute to the SLB formation process on TiO2 has been lacking and addressing this gap is important to design functional lipid biointerfaces with tailored properties such as antifouling capabilities. Herein, we investigated inverse PC lipid vesicle adsorption onto TiO2 and SiO2 surfaces and discovered how adsorption pathways can be controlled by tuning the balance of noncovalent and covalent forces, which enabled us to establish molecular design rules to fabricate physically robust SLB coatings on macroscopically flat TiO2 surfaces. On TiO2, SLB formation depended on two key factors: (1) favorable noncovalent forces to facilitate initial vesicle adsorption; and (2) a critical density of lipid-TiO2 covalent bonds to enable sufficient vesicle deformation triggering fusion and rupture. In other cases, either no adsorption or intact vesicle adsorption without rupture occurred even when covalent bonds were present. Conversely, on SiO2, conditions were identified to support inverse PC lipid adsorption whereas vesicles were repelled otherwise. The experimental results were supported by interfacial force modeling and our findings demonstrate how a subtle interplay of noncovalent and covalent forces plays a deterministic role in modulating lipid self-assembly pathways. Specific conditions in which the physically stable, fabricated SLBs on TiO2 surfaces exhibit antifouling properties were also identified based on optimizing the lipid composition to enhance vesicle-surface interactions while preventing other nonspecific interaction events.