Semisynthetic Ferritin Nanocages for Flexible, Site-Specific Targeting and Ligand-Free Activation of Membrane Receptors

Authors:

Andreas Neusch, Christina Siepe, Liesa Zitzke, Alexandra C. Fux, Cornelia Monzel

Keywords:

membrane receptors; ferritin; nanoparticle; targeting; CD95; TfR1

Abstract:

Homopolymerization and cluster formation of cellular membrane receptors (MRs) are increasingly recognized as an essential facet of cell signaling and modulator of physiological responses. Yet, there is a lack of tools that can mediate precise stimulation to better understand the mechanisms and effects of clustering. Here, we designed fluorescent semisynthetic nanoparticles (NPs) based on the iron-storage protein ferritin and Staphylococcus aureus protein A to specifically target and activate distinct MRs, without causing side-effects. The NP exhibits high monodispersity and is readily equipped with a variety of antibodies with a K_D value below 5 nM. Specificity of the NP antigen recognition was evaluated for cells expressing transferrin receptor 1 (TfR1) or the death receptor CD95, both of which displayed NP-mediated cluster formation. Finally, our engineered NP acts as a natural ligand for TfR1 and induces apoptosis signaling solely by CD95 cluster formation in a ligand-independent manner.

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