Probing the Interactions of Perfluorocarboxylic Acids of Various Chain Lengths with Human Serum Albumin: Calorimetric and Spectroscopic Investigations
Open accessAbstract
Despite an exponential increase in PFAS research over the past two decades, the mechanisms behind how PFAS cause adverse health effects are still poorly understood. Protein interactions are considered a significant driver of bioaccumulation and subsequent toxicity from re-exposure; however, most of the available literature is limited to legacy PFAS. We utilized microcalorimetric and spectroscopic methods to systematically investigate the binding between human serum albumin (HSA) and perfluorocarboxylic acids (PFCAs) of varying chain lengths and their nonfluorinated fatty acid (FA) counterparts. The results reveal the optimal chain length for significant PFCA-HSA binding and some fundamental interactions, i.e., the polar carboxylic head of PFCA is countered by ionizable amino acids such as arginine, and the fluorocarbon tails stabilized by hydrophobic residues like leucine and valine. Additionally, fluorine's unique polarizability contributes to PFCA's stronger binding affinities relative to the corresponding fatty acids. Based on these observations, we posit that PFCAs likely bind to HSA in a "cavity-filling" manner, provided they have an appropriate size and shape to accommodate the electrostatic interactions. The results reported herein widen the pool of structural information to explain PFAS bioaccumulation patterns and toxicity and support the development of more accurate computational modeling of protein-PFAS interactions. TOC graphic created with Biorender.com.
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PFCAs and PFSAs can bind to human serum albumin and other transporters in the blood.
“Moreover, they can bind to human serum albumin and other transporters in the blood [57].”
From The EU’s Per- and Polyfluoroalkyl Substances (PFAS) Ban: A Case of Policy over Science (2023) · cites this paper as [57]
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- Authors
- Crisalli, A. M., Cai, A., & Cho, B. P.
- Affiliations
- University of Rhode Island (US)
- Corresponding author
- Cho, Bongsup P.
- Venue
- Chemical Research in Toxicology
- Publisher
- American Chemical Society (ACS)
- Published
- 2023-03-31
- Volume
- 36
- Issue
- 4
- Pages
- 703-713
- ISSN
- 0893-228X (ISSN-L)
- 1520-5010
- PMC
- PMC11091765
- OpenAlex
- W4362458567
- Cited by
- 40
- References
- 60
- Citations by year
- 2026: 10 · 2025: 20 · 2024: 8 · 2023: 2
- FWCI
- 3.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Chemical Research in Toxicology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Journal of Media Literacy Education (submittedVersion, cc-by)
- Funders
- National Institute of Environmental Health Sciences (P42ES027706)
- Topics
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Interaction Studies and Fluorescence Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- perfluorocarboxylic acids, human serum albumin, protein-ligand binding, chain length effects, fatty acid analogs, bioaccumulation, PFAS toxicity, electrostatic interactions, hydrophobic interactions, microcalorimetry
- MeSH terms
- Serum Albumin, Human, Amino Acids, Calorimetry, Carboxylic Acids, Fatty Acids, Fluorocarbons, Humans, Spectrometry, Fluorescence
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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