New imaging method reveals how toxic metals infiltrate and damage human cells
Researchers have developed a technique to watch toxic metals move inside living cells and change their chemical form—without destroying the cells in the process. The breakthrough could accelerate drug development and help regulators assess environmental health risks from metal exposure in industries ranging from manufacturing to medicine.
Originaltitel: Correlative X-ray spectromicroscopy for quantitative cerium speciation in mammalian cells
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.