Abstract

The first step into assessing the nanoparticle (NP) cytotoxicity requires a thorough understanding of the NP-membrane interaction mechanism. The main aim of this study is to investigate the relationship of the surface hydrophobicity distribution of the NP with its translocation efficiency. Two types of NPs, one with a random and one with a striped hydrophobic-hydrophilic surface pattern, are investigated using Molecular Dynamics (MD) simulations and free-energy calculations. The MARTINI coarse-grained description is employed. The results illustrate the significance of the NP surface chemistry pattern by revealing that an ordered distribution of surface hydrophilic groups gives rise to generically different behavior to that of a NP with randomly placed surface hydrophilic groups. The stripedpatterned NP prefers to adopt an interfacial positioning on the membrane, whereas the random-patterned NP gets ‘ trapped’ within the lipid bilayer. From an inverse engineering point of view, the present study provides insight into the surface design of NPs with tailored functionalities, such as direct cellular entry and maximization of cellular uptake.

Keywords: molecular dynamics simulations, coarse-grained models, nanoparticle-membrane interactions, computer simulations, MARTINI, free energy calculations, Coarse-grained simulations, lipid bilayers, molecular dynamics, MARTINI force-field, nanoparticles