Discriminative adsorption of amphiphilic monolayer protected gold nanoparticles on amyloid fibers

This thesis presents a systematic study of how different types monolayer-protected AuNPs interact with amyloid fibers. We report a class of amphiphilic gold nanoparticles capable of adsorbing onto specific surface features on these types of protein fibers. A common disease-associated protein fold is the amyloid state: it is characterized by a cross-beta sheet structure that forces proteins and peptides into a fibrillar state, commonly found in illnesses such as Alzheimerâ s disease, Parkinsonâ s disease among many others. Amyloid diseases are typically chronic, correlated with ageing and have posed several challenges: the exact structure of the fibers is difficult to determine and their etiologic role is often unclear. This thesis shows, for the first time, that amphiphilic monolayer-protected AuNPs can discriminatively adsorb onto surface features of amyloid fibers made of A1-40 and -synuclein in vitro and that hydrophobicity determines adsorption onto Tau fibers. Given an amyloid fiber that adopts a twisted ribbon morphology, AuNPs protected by a mixture of sulfonated and hydrophobic thiolate molecules adsorb onto specific features on the surface of the fiber, leaving other interfaces uncovered. This generates a novel supra-molecular assembly that directly interfaces an engineered nanomaterial with a biological structure, without using antibodies. Experiments and calculations demonstrated the importance of nanoparticle size and ligand-shell composition: a size cut-off around 4 nm was observed and other types of water soluble nanoparticles did not adsorb discriminatively. Small amphiphilic AuNPs act as surfactants and probably adsorb onto solvent-exposed beta sheets and small amyloidogenic oligomers. The results presented in this thesis provide a systematic framework to understand the interaction between nanoparticles and amyloid fibers. The particles can, moreover, become useful markers for amyloid research and possibly a cross-instrumental probe to reconcile spectroscopic and imaging techniques to help molecular structure determination. During this work, the synthesis and purification of large amounts of sulfonated thiolate molecules was systematized to generate libraries of differently coated water soluble gold nanoparticles (AuNPs). This helped elucidate how amphiphilic AuNPs fuse with lipid bilayers.