An Atomistic Molecular Dynamics Study of Titanium Dioxide Adhesion to Lipid Bilayers.

Titanium dioxide (TiO2) nanoparticles are found in an array of consumer and industrial products, and human exposure to these nanoparticles involves interaction with biological membranes. To understand the effect of the membrane lipid composition on bilayer perturbation by TiO2, we performed all-atom molecular dynamics simulations of nanosized TiO2 interacting with three single component bilayers differing only in their headgroup composition: the zwitterionic DOPC, which is overall neutral containing negatively charged phosphate and positively charged choline in its head, DOPG, which is overall anionic containing negatively charged phosphate and neutral glycerol, and the anionic DOPS, containing negatively charged phosphate attached to the hydroxyl side-chain of the amino acid, serine containing negatively charged carboxyl and positively charged ammonium. The nanoparticle adheres to all three bilayers causing a negative curvature on their top leaflet. However, the local deformation of DOPG was more pronounced than DOPC and DOPS. The anionic DOPG, which is the thinnest of the three bilayers, interacted most strongly with the TiO2. DOPS has the next strongest interaction; however, its high bending modulus enables it to resist deformation by the nanoparticle. DOPC has the weakest interaction with the nanoparticle of the three as it has the highest bending modulus and its zwitterionic head groups have strong cohesive interactions. We also observed a nonuniform response of the bilayers: the orientational order of the lipids near the nanoparticle decreases, while that of the lipids away from the nanoparticle increases. The overall thickness and bending modulus of DOPG increased upon contact with the nanoparticle owing to overall stiffening of the bilayer despite local softening, while the average structural and mechanical properties of DOPC and DOPS remain unchanged, which can be explained in part by the greater bilayer bending elasticicty of DOPC and DOPS. The above findings suggest that regions of biological membranes populated by anionic lipids with weaker bending elasticity will be more susceptible to perturbation by TiO2 nanoparticles than zwitterionic-rich regions.