Development of a bottom-up coarse-grained model for interactions of lipids with TiO 2 $$ {}_2 $$ nanoparticles.

Understanding interactions of inorganic nanoparticles with biomolecules is important in many biotechnology, nanomedicine, and toxicological research, however, the size of typical nanoparticles makes their direct modeling by atomistic simulations unfeasible. Here, we present a bottom-up coarse-graining approach for modeling titanium dioxide (TiO 2 $$ {}_2 $$ ) nanomaterials in contact with phospholipids that uses the inverse Monte Carlo method to optimize the effective interactions from the structural data obtained in small-scale all-atom simulations of TiO 2 $$ {}_2 $$ surfaces with lipids in aqueous solution. The resulting coarse-grained models are able to accurately reproduce the structural details of lipid adsorption on different titania surfaces without the use of an explicit solvent, enabling significant computational resource savings and favorable scaling. Our coarse-grained simulations show that small spherical TiO 2 $$ {}_2 $$ nanoparticles ( r = 2 $$ r=2 $$ nm) can only be partially wrapped by a lipid bilayer with phosphoethanolamine headgroups, however, the lipid adsorption increases with the radius of the nanoparticle. The current approach can be used to study the effect of the size and shape of TiO 2 $$ {}_2 $$ nanoparticles on their interactions with cell membrane lipids, which can be a determining factor in membrane wrapping as well as the recently discovered phenomenon of nanoquarantining, which involves the formation of layered nanomaterial-lipid structures.