Computational Investigation of Nanoparticles at the Biointerface

Molecular self-assembly is a topic attracting intense scientific interest. Various strategies have been developed for construction of molecular aggregates with rationally designed properties, geometries, and dimensions which are able to provide solutions to both theoretical and practical problems in areas such as drug delivery, medical diagnostics, and biosensors, to name but a few. In this respect, gold nanoparticles (AuNPs) with core diameters in the rage 1−10 nm have emerged as a powerful class of materials for a variety of biomedical applications. The utility of AuNPs is enhanced by our ability in tuning their surface properties by grafting multiple ligand species able to self-assemble in mixed-monolayers. Thus, identification of molecular designing rules is essential to achieve a precise control of specifically patterned monolayer protected nanoparticles for an intended biological outcome. In this thesis are described the evidences of our investigation of the self-organization of different mixtures of immiscible ligands on a spherical gold surface. The evaluation of the role of some critical parameter such as core dimension, different chemistry and relative ligand length and ratio as well as solvent was the starting point to develop a standard procedure to tune the self-assembled monolayer (SAM) morphology. Studies of the morphology of these mixed monolayers were carried out using an in-silico approach based on multiscale molecular simulations. Then, combining theory and experiments, we investigated the role of ligand arrangement and composition on the interaction with model lipid bilayer (either simple and complex) and with cells of these monolayer protected NPs. In-silico models were then employed to study the binding of patterned AuNps with human serum albumin (HSA), uncovering the impact of the monolayer morphologies on protein-NP interfaces. Laslty, a third kind of biointerface was taken into account and the supramolecular binding of small molecules, toward mixed/homoligand shells was disclosed.