Amyloid aggregation at solid-liquid interfaces: Perspectives of studies using model surfaces

The aggregation of proteins and peptides into cytotoxic oligomeric and fibrillar amyloid aggregates represents an important mechanism in the development of numerous degenerative diseases such as Alzheimer's disease, Parkinson's disease, and type 2 diabetes mellitus. Amyloid aggregation is notoriously hard to control both in vivo and in vitro, because aggregation kinetics, aggregate morphology, and molecular aggregate structure are influenced by a multitude of environmental parameters, including monomer concentration, ionic strength, temperature, pH, and the presence of interfaces. While for a long time, amyloid aggregation has been studied mostly in bulk solution, surface and interface-related effects have recently become the focus of intense research efforts. Understanding the complex influences that solid-liquid interfaces exert on the aggregation of amyloidogenic proteins and peptides not only promises deeper insights into the molecular mechanisms of in-vivo membrane toxicity, but may also result in novel therapeutic approaches utilizing for instance amyloid-inhibiting nanoparticles. A particularly important route toward this goal is represented by studies using model surfaces with well-defined physicochemical properties in order to elucidate the involved physical and chemical mechanisms and interactions on a molecular level. This perspective article will provide an overview over the experimental techniques and model surfaces that so far have been utilized in such studies, summarize the obtained findings and insights, and address future challenges.