Modeling the reaction mechanism of membrane penetration by striated amphiphitic gold nanoparticles

Abstract

The desire to desire targeted drug delivery devices capable of releasing therapeutic payloads within the cytosol of cells has led to research on nanoparticles as suitable drug carriers. Recently, it was shown that gold nanoparticles coated in striped, alternating layers of hydrophobic and hydrophilic ligands are capable of non-disruptively penetrating a lipid bilayer, a discovery with potential implications in drug delivery. While the reaction mechanism is not known, initial experimental results indicate that endocytosis and membrane poration could be ruled as possible mechanisms. In this work, we explore the reaction mechanism of membrane penetration using a coarse-grained Brownian Dynamics model. We also define a Monte Carlo simulation for modeling ligand motion on the nanoparticle surface based on a single order parameter, and describe a method for approximating the interaction energy with the bilayer as a function of this parameter. Our simulations demonstrate the dependence of nanoparticles penetration on the surface mobility, not explicit conformation, of coated ligands. They demonstrate that while nanoparticles with static ligands in a striped conformation are unable to penetrate the bilayer, enabling surface mobility allows penetration by the induced formation of a small, transient pore of a comparable size to the nanoparticle. Our results offer an enhanced understanding of the nanoparticles-bilayer interaction and an identification of the property necessary for membrane penetration.