Year: 2026
Type: preprint
Abstract: Determining intracellular metal oxidation state and speciation in intact mammalian cells remains a major analytical challenge, as most imaging methods lack chemical specificity or require disruptive sample preparation. Using cerium (Ce) as a model lanthanide relevant to environmental and biomedical exposures, we introduce a correlative X-ray spectromicroscopy workflow enabling oxidation state determination and quantitative mapping of f-elements in whole cells. Ce toxicity, uptake, and homeostasis in human lung cancer cells (A549) were characterized by scanning transmission X-ray microscopy (STXM), ptychography, bright-field transmission electron microscopy (BF-TEM) and viability assays across three sample preparations-chemically fixed, cryogenically preserved, and resin-embedded/microtomed cells. Ce was found to be membrane-bound and internalized, predominantly in the +3 oxidation state. EXAFS analysis indicates mononuclear or cluster-like coordination without precipitate formation. Active uptake processes drive Ce internalization, with intracellular Ce localized in autophagosomes and autolysosomes after 24 hours. Beyond elucidating Ce toxicity mechanisms, this correlative workflow is broadly applicable to lanthanides, actinides, and other redox-active metals for studying intracellular metal speciation in biological systems.
Source: ChemRxiv
Authors: Bianca Schacherl, Adedamola Arojojoye, Abhyavartin Selvam, Jacob A Branson, Trevor Arino, Danielle M Jorgens, Misun Kang, Jian Wang, Alexander S Ditter, Hendrick Ohldag, David Shapiro, Konstantin Klemetiev, Corwin H Booth, Tatjana Paunesku, David K. Shuh, Rebecca J Abergel, Stefan G Minasian
Language: English
Subfield: Radiation
Field: Physics and Astronomy
Domain: Physical Sciences
Open Access status: green
Funders: U.S. Department of Defense, U.S. Department of Energy, VINNOVA, Svenska Forskningsrådet Formas, Vetenskapsrådet, National Institutes of Health, Office of Science, Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, National Institute of Allergy and Infectious Diseases, Basic Energy Sciences, Chemical Sciences, Geosciences, and Biosciences Division, Lawrence Berkeley National Laboratory
Awards: G1079818582, G1143651532, G1286236842, G1286251239, G16587699, G2037563265, G208125138, G2795275917, G30714459, G3083819904, G317939215, G3728818118, G382641700, G4061288673, G4119534169, G419881185, G42916606, G4501827968, G498139845, G5096929151, MAX IV operations – Formas, G5224014036, G5229471624, ALIGNING DOSIMETRY AND BIOMARKERS OF LUNG INJURY WITH PROPHYLAXIS AND MITIGATION OF DAMAGE FROM RADIONUCLIDES AND METALS, G5850682332, G594270511, G650090426, G712881263, G7354628648, MAX IV operations 2019-2021, Multi-Scale Evaluation and Mitigation of Toxicities Following Internal Radionuclide Contamination, G969889393
OpenAlex ID: W7129601963