Interrogating ligand-receptor interactions using highly sensitive cellular biosensors

Maximilian A. Funk, Judith Leitner (), Marlene C. Gerner, Jasmin M. Hammerler, Benjamin Salzer, Manfred Lehner, Claire Battin, Simon Gumpelmair, Karin Stiasny, Katharina Grabmeier-Pfistershammer and Peter Steinberger ()
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Maximilian A. Funk: Medical University of Vienna
Judith Leitner: Medical University of Vienna
Marlene C. Gerner: University of Applied Sciences FH Campus Wien
Jasmin M. Hammerler: University of Applied Sciences FH Campus Wien
Benjamin Salzer: St. Anna Children’s Cancer Research Institute
Manfred Lehner: St. Anna Children’s Cancer Research Institute
Claire Battin: Medical University of Vienna
Simon Gumpelmair: Medical University of Vienna
Karin Stiasny: Medical University of Vienna
Katharina Grabmeier-Pfistershammer: Medical University of Vienna
Peter Steinberger: Medical University of Vienna

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract Interactions of membrane-resident proteins are important targets for therapeutic interventions but most methods to study them are either costly, laborious or fail to reflect the physiologic interaction of membrane resident proteins in trans. Here we describe highly sensitive cellular biosensors as a tool to study receptor-ligand pairs. They consist of fluorescent reporter cells that express chimeric receptors harboring ectodomains of cell surface molecules and intracellular signaling domains. We show that a broad range of molecules can be integrated into this platform and we demonstrate its applicability to highly relevant research areas, including the characterization of immune checkpoints and the probing of cells for the presence of receptors or ligands. The platform is suitable to evaluate the interactions of viral proteins with host receptors and to test for neutralization capability of drugs or biological samples. Our results indicate that cellular biosensors have broad utility as a tool to study protein-interactions.

Date: 2023
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DOI: 10.1038/s41467-023-43589-1

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