The Effect of PFOA on the Secondary Structure and Hydration of Globular Proteins: A CD and 2D-IR Study

Per- and polyfluoroalkyl substances (PFAS) are present in human blood at concentrations that lead to health risks. Despite the urgency to understand the molecular mechanism underlying PFAS toxicity, studies on the interaction of proteins with PFAS are still scarce. Here, we combine circular dichroism with linear and two-dimensional infrared spectroscopy to investigate the effect of perfluorooctanoic acid (PFOA) on the structure and hydration of three different globular proteins. We find that the investigated proteins undergo structural changes only at high (≥100µM), biologically non-relevant PFOA concentrations. Interestingly, however, we observe a change in the hydration shell of serum albumin that may also occur at biologically relevant PFOA concentrations, indicating that water:protein interactions are affected by PFOA. Our results thus suggest that PFAS does not affect the protein secondary structure but disrupts specific interactions between proteins and their environment, which may play a role in the toxicity of PFAS.