Molecular-level characterization of the interaction between monolayer-protected Au nanoparticles and model lipid membranes and proteins

In this thesis we study the interactions of monolayer-protected gold nanoparticles with proteins and model lipid membranes. Gold nanoparticles are a paradigm in biological applications of nanomaterials, thanks to their peculiar physico-chemical properties; among these, the possibility to bind different kinds of molecules (ligands) to gold atoms in clusters via thiol bonds is particularly important for biomedical use of nanoparticles. In fact, the ligand shell is what nanoparticles expose to the biological environment in which they are used. In in vivo applications, nanoparticles come in contact with many biological molecules before being delivered to cells, which are the target of most of biological applications of nanoparticles. Among them, proteins are particularly relevant since they can irreversibly bind to nanoparticles, thus changing the surface they expose to the biological environment. In this thesis we use molecular dynamics simulations to study how different ligands can influence the interaction of nanoparticles with the most abundant protein in blood, human serum albumin. We test two zwitterionic ligands with different hydrophobic content and we find that ligand conformation, which is affected by hydrophobicity, promotes different adhesion strengths between nanoparticles and albumin. We then study the interaction of nanoparticles with a model cell membrane, the first barrier they encounter in cell-targeted applications. We use molecular dynamics simulations to study the mechanism of interaction between a negatively charged nanoparticle and a neutral lipid membrane. We find that the process develops in three stages which involves the adsorption on the membrane surface and the progressive penetration in the membrane core of the nanoparticle. Finally, we study the influence of the sign of the charge on nanoparticles on their interaction with a model membrane. We use experiments of fluorescent dye-leakage from neutral liposomes to probe the effect of positively and negatively charged nanoparticles on the model membrane of the lipid vesicles. In particular, we find that both anionic and cationic nanoparticles behave similarly in the interaction with a zwitterionic lipid membrane. We use molecular dynamics simulations to support the experimental findings and observe that anionic and cationic nanoparticles share similar interaction processes and energetics.