We use coarse-grained molecular dynamics simulations to "observe" details of interactions between ligand-covered gold nanoparticles and a lipid bilayer model membrane. In molecular dynamics simulations, one puts the individual atoms and groups of atoms of the physical system to be "observed" into a simulation box, specifies the forms of the potential energies of interactions between them (ultimately quantum based), and lets them individually move classically according to Newton's equations of motion, based on the forces arising from the assumed potential energy forms. The atoms that are chemically bonded to each other stay chemically bonded, following known potentials (force fields) that permit internal degrees of freedom (internal rotation, torsion, vibrations), and the interactions between nonbonded atoms are simplified to Lennard-Jones forms (in our case) and coulombic (where electrical charges are present) in which the parameters are previously optimized to reproduce thermodynamic properties or are based on quantum electronic calculations. The system is started out at a reasonable set of coordinates for all atoms or groups of atoms, and then permitted to develop according to the equations of motion, one small step (usually 10 fs time step) at a time, for millions of steps until the system is at a quasi-equilibrium (usually reached after hundreds of nanoseconds). We then let the system play out its motions further for many nanoseconds to observe the behavior, periodically taking snapshots (saving all positions and energies), and post-processing the snapshots to obtain various average descriptions of the system. Alkanethiols of various lengths serve as examples of hydrophobic ligands and methyl-terminated PEG with various numbers of monomer units serve as examples of hydrophilic ligands. Spherical gold particles of various diameters as well as gold nanorods form the core to which ligands are attached. The nanoparticles are characterized at the molecular level, especially the distributions of ligand configurations and their dependence on ligand length, and surface coverage. Self-assembly of the bilayer from an isotropic solution and observation of membrane properties that correspond well to experimental values validate the simulations. The mechanism of permeation of a gold NP coated with either a hydrophobic or a hydrophilic ligand, and its dependence on surface coverage, ligand length, core diameter, and core shape, is investigated. Lipid response such as lipid flip-flops, lipid extraction, and changes in order parameter of the lipid tails are examined in detail. The mechanism of permeation of a PEGylated nanorod is shown to occur by tilting, lying down, rotating, and straightening up. The nature of the information provided by molecular dynamics simulations permits understanding of the detailed behavior of gold nanoparticles interacting with lipid membranes which in turn helps to understand why some known systems work better than others and aids the design of new particles and improvement of methods for preparing existing ones.
Keywords: Gold nanoparticles; Gold nanorod; Membrane permeation; Molecular dynamics simulations; PEGylated.