ArticleScience advances2024
Advanced multiparametric image spectroscopy and super-resolution microscopy reveal a minimal model of CD95 signal initiation.
Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Realizing the potential of agonistic antibody immunotherapy.Nature reviews. Drug discovery · 2026Review
- Superparamagnetic Biomembranes for Dynamic Nanoparticle and Molecular Patterning.Nano letters · 2026Article
- Semisynthetic Ferritin Nanocages for Flexible, Site-Specific Targeting and Ligand-Free Activation of Membrane Receptors.Nano letters · 2025Article
- CD95/Fas stoichiometry in future precision medicine.Cell death and differentiation · 2025Review
- High yield purification of an isoleucine zipper-modified CD95 ligand for efficient cell apoptosis initiation and with biotin or DNA-oligomer binding domain to probe ligand functionalization effects.BMC biotechnology · 2025Article
- Effects of DNA Origami-Based Nanoagent Design on Apoptosis Induction in a Large 3D Cancer Spheroid Model.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
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Authors and funding
10 authors.
Funding
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Abstract
Unraveling the concentration-dependent spatiotemporal organization of receptors in the plasma membrane is crucial to understand cell signal initiation. A paradigm of this process is the oligomerization of CD95 during apoptosis signaling, with different oligomerization models being discussed. Here, we establish the molecular-sensitive approach cell lifetime Förster resonance energy transfer image spectroscopy to determine CD95 configurations in live cells. These data are corroborated by stimulated emission depletion microscopy, confocal photobleaching step analysis, and fluorescence correlation spectroscopy. We probed CD95 interactions for concentrations of ~10 to 1000 molecules per square micrometer, over nanoseconds to hours, and molecular to cellular scales. Quantitative benchmarking was achieved establishing high-fidelity monomer and dimer controls. While CD95 alone is primarily monomeric (~96%) and dimeric (4%), the addition of ligand induces oligomerization to dimers/trimers (~15%) leading to cell death. This study highlights molecular concentration effects and oligomerization dynamics. It reveals a minimal model, where small CD95 oligomers suffice to efficiently initiate signaling.
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