Influence of Substrate Hydrophilicity on Structural Properties of Supported Lipid Systems on Graphene, Graphene Oxides, and Silica.

Pristine graphene, a range of graphene oxides, and silica substrates were used to investigate the effect of surface hydrophilicity on supported lipid bilayers by means of all-atom molecular dynamics simulations. Supported 1,2-dioleoyl-sn-glycero-3-phosphocholine lipid bilayers were found in close-contact conformations with hydrophilic substrates with as low as 5% oxidation level, while self-assembled monolayers occur on pure hydrophobic graphene only. Lipids and water at the surface undergo large redistribution to maintain the stability of the supported bilayers. Deposition of bicelles on increasingly hydrophilic substrates shows the continuous process of reshaping of the supported system and makes intermediate stages between self-assembled monolayers and supported bilayers. The bilayer thickness changes with hydrophilicity in a complex manner, while the number of water molecules per lipid in the hydration layer increases together with hydrophilicity.

Low-Density Lipoproteins and Human Serum Albumin as Carriers of Squalenoylated Drugs: Insights from Molecular Simulations.

We have studied the interaction of three clinically promising squalenoylated drugs (gemcitabine-squalene, adenine-squalene, and doxorubicin-squalene) with low-density lipoproteins (LDL) by means of atomistic molecular dynamics simulations. It is shown that all studied squalenoylated drugs accumulate inside the LDL particles. This effect is promoted by the squalene moiety, which acts as an anchor and drives the hydrophilic drugs into the hydrophobic core of the LDL lipid droplet. Our data suggest that LDL particles could be a universal carriers of squalenoylated drugs in the bloodstream. Interaction of gemcitabine-squalene with human serum albumin (HSA) was also studied by ensemble of docking simulations. It is shown that HSA could also act as a passive carrier of this bioconjugate. It should be noted that the binding of squalene moiety to HSA was unspecific and did not occur in the binding pockets devoted to fatty acids.