The role of surfaces on amyloid formation

Interfaces can strongly accelerate or inhibit protein aggregation, destabilizing proteins that are stable in solution or, conversely, stabilizing proteins that are aggregation-prone. Although this behaviour is well-known, our understanding of the molecular mechanisms underlying surface-induced protein aggregation is still largely incomplete. A major challenge is represented by the high number of physico-chemical parameters involved, which are highly specific to the considered combination of protein, surface properties, and solution conditions. The key aspect determining the role of interfaces is the relative propensity of the protein to aggregate at the surface with respect to bulk. In this review, we discuss the multiple molecular determinants that regulate this balance. We summarize current experimental techniques aimed at characterizing protein aggregation at interfaces, and highlight the need to complement experimental analysis with theoretical modelling. In particular, we illustrate how chemical kinetic analysis can be combined with experimental methods to provide insights into the molecular mechanisms underlying surface-induced protein aggregation, under both stagnant and agitation conditions. We summarize recent progress in the study of important amyloids systems, focusing on selected relevant interfaces.

Automated summary

Interfaces can have a significant impact on protein aggregation behavior, with the molecular mechanism behind this process still not fully understood due to numerous physico-chemical parameters at play. The key factor determining protein aggregation at interfaces is the relative propensity compared to bulk phases. Combining experimental techniques with theoretical modeling is essential for gaining insights into the molecular mechanisms underlying surface-induced protein aggregation.