Charge and hydrophobicity effects at nano-bio interfaces

Gold nanoparticles coated with bio-compatible ligands are promising tools for biomedical applications due their water solubility, bio-compatibility and efficient light-to-heat conversion. In in vivo applications, nanoparticles come in contact with many biological molecules before being delivered to cells. The understanding of the physical and chemical nature of these different nano-bio interfaces is crucial to the rational design of nanoparticles with biomedical applications. The aim of this thesis is to understand, by molecular dynamics, how the composition, hydrophobicity and charge of the ligand shell of a small gold nanoparticle can influence its interaction with i. the solvent, ii. model biological membranes and iii. serum proteins. For each of these relevant interfaces we address a specific case of study. In our first case study, we address the role of ligands during the transfer of heat from a hot irradiated gold nanoparticle to the surrounding solvent (water). Indeed, in photothermal therapies laser-irradiated resonant nanoparticles convert light into heat, which is then released to the surrounding biological tissues. Nevertheless, no clear physical interpretation is currently available to explain thermal transport at the nanoparticle surface, where a solid-liquid (metal--ligand) interface is coupled to a liquid-liquid (ligand--solvent) interface. We use computer simulations to show that thermal transport at the nanoparticle surface depends on solvent diffusivity at the ligand--solvent interface. Furthermore, using physical indicators of water confinement around hydrophobic and hydrophilic ligands, we develop a predictive model to allow engineering of nanoparticle coatings with the desired thermal conductivities at the nanoscale. The second case study is the interaction between an anionic, monolayer-protected gold nanoparticle and a model neutral lipid membrane. The cell membrane is the first barrier that gold nanoparticles meet in cell-targeted applications. Here we show how the nanoparticle surface functionalization, and in particular its charge state, can drive the mechanism of interaction with a zwitterionic lipid membrane. Our third case study is the interaction between a monolayer-protected gold nanoparticle and a serum protein, ubiquitin. Indeed, when nanoparticles circulate in the bloodstream, they come in contact with many serum proteins, which can irreversibly bind to nanoparticles, thus changing the surface they expose to the biological environment. We combine computer simulations and experimental results to study how the ligand charge and composition influence the interaction between nanoparticles and ubiquitin. We find that interfacial water molecules are more bound to the nanoparticles with the largest negative charge and this reflects in an increase of their hydrodynamic radius and in a slower kinetics of binding to the protein during unbiased simulations.