Hydrophobic interfaces are ubiquitous, and interactions of proteins with such surfaces remain an area of significant interest. α-Synuclein (α-Syn), a protein abundant in cerebrospinal fluid, is implicated in nearly 50 neurological disorders. The misfolding of α-Syn into amyloid aggregates is a critical step in the progression of several neurodegenerative diseases. Hydrophobic interfaces have been shown to catalyze this process. To better understand the mechanism of aggregation and ultimately aid in the development of therapeutic strategies, it is essential to probe the interfacial structures of α-Syn that may drive amyloid formation. Here, we present a detailed investigation of the interfacial structure of α-Syn on a polystyrene (PS) film, a widely used material in consumer products and laboratory settings. Elucidating the structural motifs of α-Syn at the PS interface provides insights into how plastic contaminants may induce conformational changes in the protein. Combining experimental vibrational sum frequency generation spectroscopy with theoretical spectral calculations, we identify the interfacial structure of α-Syn at the PS film and compare it with previously reported α-Syn conformation on air-water interfaces. The entire NAC region and majority of the residues in the N terminal are in direct contact with the PS surface, while the C terminal residues protrude away from the interface, staying in the solution. Our studies highlight the critical role of polymeric surfaces in facilitating α-Syn misfolding.
Mishra et al. (2026) studied this question.