Deriving Membrane-Water and Protein-Water Partition Coefficients from In Vitro Experiments for Per- and...

Area of Science:

• Environmental Chemistry
• Toxicology
• Biochemistry

Background:

• Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants with complex distribution patterns in biological systems.
• Understanding PFAS partitioning between biological membranes and proteins like human serum albumin (HSA) is crucial for assessing bioaccumulation and toxicity.

Purpose of the Study:

• To quantify the phospholipid membrane-water partition coefficients (KMW) and HSA binding affinities for diverse PFAS.
• To evaluate the predictive capability of molecular docking for HSA-PFAS interactions.
• To model exposure-dependent PFAS partitioning in organisms.

Main Methods:

• Laboratory measurements of KMW and HSA binding affinities for 60 PFAS.
• Molecular docking simulations using AutoDock Vina to predict HSA-PFAS binding.
• In vitro modeling of PFAS partitioning based on distribution coefficients at varying concentrations.

Main Results:

• PFAS KMW increased with fluorinated carbon chain length for both carboxylic acids and sulfonates.
• HSA affinity was highest for PFAS with C6-C10 chains, with specific structural subclasses showing greater affinity.
• Molecular docking accurately predicted HSA-PFAS affinity for shorter chain lengths (C4-C10).
• At low concentrations, PFAS preferentially partitioned to HSA; at higher concentrations, partitioning shifted to phospholipid membranes.

Conclusions:

• PFAS partitioning is concentration-dependent, shifting from protein binding to membrane accumulation as exposure increases.
• Protein-water distribution coefficients are higher than membrane-water partitioning coefficients at lower PFAS concentrations.
• These findings have significant implications for interpreting PFAS exposure data and toxicity studies.