# Bioaccumulation of PFOS Isomers in Transporter Proteins

## TL;DR

This study shows that branched isomers of PFOS accumulate more in transporter proteins than linear ones, using simulations and experiments.

## Contribution

The study reveals the bioaccumulation potential of branched PFOS isomers in transporter proteins through molecular dynamics simulations.

## Key findings

- Branched PFOS isomers show higher bioaccumulation potential than linear isomers in LCFA transport proteins.
- Binding interactions with residues ARG_157 and GLU_319 influence PFOS isomer accumulation.
- The position of −CF3 substitutions in branched isomers affects their bioaccumulation potential.

## Abstract

The many-decade use of perfluorooctanesulfonic acid (PFOS)
in firefighting
foams and other products has resulted in their accumulation in water
sources and terrestrial environments. Long-term exposure of PFOS has
been linked to detrimental effects on human health. PFOS, primarily
manufactured through electrochemical fluorination (ECF), yielded both
linear and branched isomers. While progress has been made in understanding
the health impacts of linear PFOS exposure on human health, there
is far less understanding about the toxicological effects and bioaccumulative
potential of their branched isomers. In this study, the bioaccumulation
potential of linear PFOS and five different branched isomers in the
long-chain fatty acid (LCFA) transport protein from Escherichia coli (E. coli) is investigated using molecular dynamics simulations. The bioaccumulative
potential of the PFOS isomers was assessed by computing their binding
strength at both the low-affinity site and the high-affinity site
in comparison with natural ligands. The binding characteristics of
PFOS isomers from in silico examinations are in good
agreement with in vitro cellular studies. Our study
demonstrates a preferential bioaccumulation potential for certain
branched isomers rather than linear PFOS. The low hydrogen bonding
network of disubstituted isomers compared to monosubstituted isomers
at the low-affinity site corroborates with their minimal abundance
in the in vitro studies. The interactions between
the PFOS isomers with residues ARG_157 and GLU_319 determine their
binding potential. Additionally, the location of −CF3 substitutions in branched PFOS isomers plays a crucial role in governing
their overall bioaccumulation potential, providing insight about the
bioaccumulation potential in living organisms.