Two-dimensional FTIR methods on amyloid aggregation and folding pathways

This chapter explores the application of two-dimensional infrared (2DIR) spectroscopy to investigate amyloid aggregation mechanisms. It details experimental strategies, including site-specific isotope labeling, to monitor residue-level kinetics and transient intermediates in amyloids. The chapter further examines polarization-resolved 2DIR and cross-peak analysis for distinguishing coexisting fibril polymorphs and quantifying secondary nucleation events. Additionally, we highlight the ability of 2DIR to detect amyloid structures in tissues. Collectively, these advancements establish 2DIR as a precise, structure-specific tool for elucidating aggregation pathways in both solution and physiologically relevant contexts.