(496c) Transport of Ions and Water and Lipid Flip-Flop During Ligand-Coated Nanoparticle Permeation in a Lipid Membrane

Nanoparticles are generally considered excellent candidates for targeted drug delivery.  However, ion and water transport and cytotoxicity induced by nanoparticle permeation is a potential problem in such drug delivery schemes because of the toxic effect of many ions.  In this study, we have carried out a series of coarse-grained molecular dynamics simulations to investigate the water penetration, ion transport, and lipid molecule flip-flop in a protein free phospholipid bilayer membrane during ligand-coated nanoparticle permeation.  The effect of ion concentration gradient, pressure differential across the membrane, nanoparticle size, length of ligand, and permeation velocity has been examined in this work.  Some conclusions from our studies include (1) The number of water molecules in the interior of the membrane during the nanoparticle permeation increases with nanoparticle size and pressure differential across the membrane but is unaffected by the nanoparticle permeation velocity or the ion concentration gradient.  (2) Ion transport is sensitive to the size of the nanoparticle as well as the ion concentration gradient between two sides of the membrane; no anion/cation selectivity is observed for small nanoparticle permeation, while anions are preferentially translocated through the membrane when the size of the nanoparticle is large enough. (3) Incidences of lipid molecule flip-flop increases with the size of the nanoparticle and ion concentration gradient and decreases with the pressure differential and nanoparticle permeation velocity.  Finally, we will also report on the effect of ligand size on water and ion leakage and the frequency and mechanism of lipid flip-flop.