Investigating PFOS-induced structural changes and aggregation in hen egg white lysozyme: spectroscopic and molecular insights.

Abstract

The widespread manufacture and use of perfluoroalkyl substances (PFAS) has jeopardized human health & environment tremendously, thereby becoming a grave cause of concern for the thriving ecosystem. The current understanding of PFAS on protein aggregation is still in the early stage. Thus, the current study investigates how Perfluorooctanesulfonic acid (PFOS) affects the Lysozyme (HEWL), a protein that typically aggregates in acidic and high temperatures. Our study employed diverse techniques, including spectroscopy, thermal analysis, and in silico modeling, to gain intriguing insights about the same. Using a combination of steady-state fluorescence spectroscopy, ITC, molecular docking, molecular dynamic simulation and circular dichroism, our study reveals strong and significant PFOS and HEWL interactions characterized by hydrogen bonding, hydrophobic forces, and ionic interactions. PFOS significantly alters the secondary structure of HEWL, as evidenced by circular dichroism and synchronous fluorescence spectroscopy. Increased PFOS concentrations caused HEWL aggregation at room temperature (25 ^ºC) and under physiological conditions (pH 7.4 and 37 ^ºC), as is substantiated through different assays. Protein aggregation was found to rapidly accelerate at 37 ^ºC, providing new insights into the process. Our findings shed light on the health risks of PFOS exposure through protein aggregation, contributing to environmental toxicology progress.