Measuring Tension At The Cell Surface

A new fluorescent sensor enables researchers to measure the force exerted by a cell membrane receptor as it binds to a target ligand. Using the molecule, Khalid S. Salaita of Emory University and coworkers demonstrate that epidermal growth factor (EGF) receptor, a protein overexpressed in a number of cancers, pulls on the peptide ligand EGF, tugging it into the cell during binding (Nat. Methods, DOI: 10.1038/nmeth.1747). To make this observation, the researchers designed the tension sensor carefully, putting a biotin moiety on one end, adding EGF and a fluorophore on the other, and connecting them with a springy polyethylene glycol (PEG) linker. Then they tethered the sensor to a glass surface coated with a quencher molecule and the protein streptavidin, which binds to the biotin. When the researchers added breast cancer cells to this sensor surface, they observed increases in fluorescence where the sensor molecules were pulled away from the surface during binding. On the basis of those increases and PEG’s well-known tension properties, the team determined the force on EGF.