Proteins on the surfaces of cells act as gateways between the cell and its surroundings. The interactions of these proteins with one another and with their ligands can be difficult to determine. A team led by Bernd Wollscheid of the Swiss Federal Institute of Technology (ETH), Zurich, and the Swiss Institute of Bioinformatics has developed a light-controlled method called LUX-MS that enables the researchers to identify proteins and ligands that are close to one another on cell surfaces (Nat. Commun. 2021, DOI: 10.1038/s41467-021-27280-x). LUX-MS works with a wider variety of ligands than previous methods do. The researchers couple ligands, such as antibodies, peptides, or small molecules, to thiorhodamine, which serves as a singlet oxygen generator when irradiated with light from a light-emitting diode. The singlet oxygen oxidizes certain amino acids, such as histidine, in nearby proteins. Proteins farther away are not oxidized. The researchers add a biotin handle to the oxidized amino acids. The biotin enables those proteins to be captured for subsequent mass spectrometric analysis. The researchers used the method to identify proteins that interact with antibodies, peptides such as insulin, and small biomolecules and drugs. They also labeled bacteria-targeting viruses and determined which proteins on the cell surface the viruses interact with.