Charge and Coordination Directed Liposome Fusion onto SiO₂ and TiO₂ Nanoparticles

TiO₂ and SiO₂ are very useful materials for building biointerfaces. A particularly interesting aspect is their interaction with lipid bilayers. Many past research efforts focused on phosphocholine (PC) lipids, which form supported lipid bilayers (SLB) on SiO₂ at physiological conditions but are adsorbed as intact liposomes on TiO₂. Low pH was required to form PC SLBs on TiO₂. This work intends to understand the surface forces and chemistry responsible for such differences. Two charge neutral lipids: 1,2-dioleoyl- sn-glycero-3-phosphocholine (DOPC) and 2-((2,3-bis(oleoyloxy)propyl)dimethylammonio)ethyl ethyl phosphate (DOCPe) and two negatively charged lipids: 1,2-dioleoyl- sn-glycero-3-phospho-l-serine (DOPS) and 2-((2,3-bis(oleoyloxy)propyl)dimethylammonio)ethyl hydrogen phosphate (DOCP) were used. Using calcein leakage assays, adsorption measurement, cryo-TEM, and washing, we concluded that charge is the dominating factor on SiO₂. The two neutral lipids form SLB on SiO₂ at pH 3 and 7, but the two negatively charged ones cannot form. On TiO₂, both charge and coordination chemistry are important. The two anionic lipids formed SLB from pH 3 to 10. DOCP had stronger affinity than DOPS likely due to the tighter terminal phosphate binding of the former. The two neutral liposomes formed SLB only at pH 3, where phosphate interaction and van der Waals force are deemed important. The pH 3 prepared TiO₂ DOPC SLBs are destabilized at neutral pH, indicating the reversible nature of the interaction. This work has provided new insights into two important materials interacting with common liposomes, which are important for reproducible biosensing, device fabrication, and drug delivery applications.