(419i) Effect of Length of Ligands on Permeation of Ions and Water and Lipid Flip-Flop in Nanoparticle Transport through a Lipid Membrane

Functionalized nanoparticles are generally considered excellent candidates for targeted drug delivery systems.  However, the ion and water leakage induced by permeation of these nanoparticles is a challenge in these drug delivery methods due to cytotoxic effects of some ions.  In this study, we have carried out a series of coarse-grained molecular dynamics simulations to investigate the effect of length of ligands on permeation of a nanoparticle across a protein free phospholipid bilayer membrane.  Water and ion penetration as well as incidence of lipid flip flop are explored in this study while varying the ion concentration gradient, pressure differential across the membrane, nanoparticle size, length of ligand, and nanoparticle permeation velocity.  Some conclusions from our studies include: (1) The number of water molecules in the interior of the membrane during ligand-coated nanoparticle permeation increases with nanoparticle size, ligand size, pressure differential, and permeation velocity but is not sensitive to the ion concentration gradient.  (2) Frequency of lipid molecule flip-flop during ligand-coated nanoparticle permeation increases with nanoparticle size, but is not sensitive to ligand size, ion concentration gradient, permeation velocity, or pressure differential.  (3) Ion transport during ligand-coated nanoparticle permeation is sensitive to the size of the nanoparticle but does not vary with ligand length, permeation velocity, or pressure differential; no anion/cation selectivity is observed for small nanoparticle permeation (2 nm), while anions are preferentially translocated through the membrane when the size of the nanoparticle increases (3 nm).  Finally, we will also report on the effect of ligand coverage on water and ion leakage and the frequency and mechanism of lipid flip-flop.