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 scarce. Here, we combine circular dichroism with linear and 2D 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 (≥1000 μM), biologically nonrelevant PFOA concentrations. Interestingly, however, we do observe evidence for a change in the hydration shell of serum albumin that may also occur at biologically relevant PFOA concentrations (≤10 μM), indicating that water:protein interactions are affected by PFOA. Our results thus suggest that PFAS do not affect the protein secondary structure but disrupt specific interactions between proteins and their environment, which may play a role in the toxicity of PFAS.
Wael et al. (Thu,) studied this question.