Interaction between Per- and poly-fluoroalkyl substances (PFAS) and Nucleic Acids

Summary Per- and poly-fluoroalkyl substances (PFAS), commonly referred to as 'forever chemicals' are pervasive environmental contaminants that present a significant risk to human health and the environment. In recent years, there has been increasing focus on investigating their toxicity and pathogenicity; however, our understanding of their toxicity remains in its early stages. Previous research has demonstrated that PFAS molecules preferentially bind to proteins in a manner correlated with the length of their carbon chains. Additionally, PFAS exposure has been shown to interfere with global and genome-wide DNA methylation. Despite these findings, significant knowledge gaps remain in our understanding of the interaction between PFAS and nucleic acids. This project aims to investigate the binding properties of commonly encountered PFAS molecules with nucleic acids of diverse nucleobase compositions by employing a series of optical and thermodynamic analysis methods. The conformational changes in nucleic acids following interaction with PFAS molecules will be investigated using circular dichroism (CD) and UV-vis spectroscopy, hydrodynamic viscosity testing, Atomic Force Microscopy (AFM) and Transmission Electron Microscopy (TEM). The binding affinity will be examined by measuring the melting temperature (Tm), binding enthalpy (ΔH), and equilibrium association constant (Ka). The stoichiometry (n) and driving force of each interaction will be assessed by analyzing Gibbs free energy (ΔG), entropy change (TΔS), and changes in constant pressure heat capacity (ΔCp) via Isothermal Titration Calorimetry (ITC). Investigating the interaction between PFAS and nucleic acids will enhance our understanding of the binding preferences of different base pairs or sequences with PFAS molecules of varying carbon-chain lengths and functional groups, as well as the impact of PFAS on the ecosystem and human health. Furthermore, this research will provide essential insights into potential therapeutic strategies, support the development of advanced biosensors for PFAS detection, and guide future material design. Project Number: 1R03ES037424-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Environmental Health Sciences (NIEHS) | Principal Investigator: Renjie Wang | Institution: FLORIDA ATLANTIC UNIVERSITY, BOCA RATON, FL | Award Amount: $146,313 | Activity Code: R03 | Study Section: Macromolecular Structure and Function B Study Section[MSFB] View on NIH RePORTER: https://reporter.nih.gov/project-details/11304438