Micromechanical measurement of membrane receptor binding for label-free drug discovery.

A potential novel binding assay based on binding-driven micromechanical motion is described. A membrane preparation containing 5-HT(3AS) receptors was used to modify a microcantilever. The modified microcantilever was found to bend on application of the naturally occurring agonist (5-hydroxytryptamine, which is also called serotonin) or the antagonist MDL-72222, but not to other similar molecules. Control experiments show that cantilevers modified by membrane preparations that do not contain 5-HT(3AS) receptors do not respond to serotonin or MDL-72222. K(d) values obtained for serotonin and MDL-72222 are identical to those obtained from radio-ligand binding assays. These results suggest that the microcantilever system has potential for use in label-free, drug screening applications.