The Impact of Forever Chemicals on Protein Structure and Function

Per- and polyfluoroalkyl substances (PFAS), commonly known as "forever chemicals," are a category of manufactured compounds that have been widely used in applications such as firefighting foams, clothing, cookware, cosmetics, and food packaging since the 1940s. These chemicals are known to bioaccumulate in many species, including humans, with half-lives numbering years and decades. Many of these chemicals are already known for their acute and chronic adverse effects on human health, and the list of confirmed harmful outcomes has continued to grow quickly. Since PFAS are persistent in the environment and everyday products, the cumulative exposure risk is quite high. Recently, PFAS have come under regulatory scrutiny, with safe exposure limit guidelines being consistently lowered as detection methods continue to improve. The majority of the research cataloging the effects of PFAS on human health have, thus far, been concentrated around the development of reliable detection methods and mitigation strategies. Only recently have efforts shifted towards investigations of how PFAS affect biomolecular function in membranes and proteins. To aid future research on PFAS interactions with biomolecules, this review summarizes the current state of knowledge about PFAS impact on the structure and function of albumins, hemoproteins, nuclear receptors, and membrane receptors.