Atomistic simulations of per- and polyfluoroalkyl substances self-assembly in water and insertion into the E. coli...

Per- and polyfluoroalkyl substances (PFAS) are widely used synthetic chemicals and persistent environmental contaminants with emerging biological toxicity. In this work, using atomistic molecular dynamics simulations, we studied the self-assembly behavior of representative PFAS, including anionic perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), as well as charge-neutral short-chain polytetrafluoroethylene (PTFE), and their insertion into the outer membrane (OM) of Escherichia coli (E. coli). PFAS self-assembly is found to be strongly governed by molecular charge, headgroup chemistry and fluorocarbon chains. Anionic amphiphilic PFOA and PFOS form micelle-like aggregates with charged headgroups exposed to water and fluorocarbon chains segregated in the core, whereas charge-neutral PTFE forms large, highly stable aggregates in aqueous solution. Electrostatic repulsion between negatively charged headgroups constrains cluster growth and reduces assembly stability, with PTFE forming more stable assemblies than PFOA and PFOS. Simulations also show that anionic PFOA and PFOS, as well as charge-neutral PTFE molecules, readily penetrate the highly hydrated outer polysaccharide layer (i.e., the O-antigen) of the E. coli OM but encounter a pronounced energetic barrier to deeper insertion into the inner region of the core oligosaccharide. Further analyses of PFOA and PTFE reveal distinct free energy profiles for their molecular insertion into the OM due to differences in charge and hydrophobicity. Our study provides molecular-level insight into PFAS self-assembly in water, which is important for PFAS removal technologies, and elucidates PFAS diffusion in the bacterial OM, which may be relevant to PFAS resistance and toxicity in E. coli and other Gram-negative bacteria.