Optical Biosensors for Monitoring Dynamic Mass Redistribution in Living Cells Mediated by Epidermal Growth Factor Receptor Activation

This paper reported the identification and mechanism of dynamic mass redistribution in living cells mediated by epidermal growth factor receptor (EGFR) activation using resonant waveguide grating (RWG) biosensors. In response to epidermal growth factor (EGF) stimulation, human epidermoid carcinoma A431 cells gave rise to a dynamic response due to dynamic mass redistribution (DMR) in the cells. The DMR response was strongly dependent on cell culture conditions and EGF concentrations. The DMR response of quiescent A431 cells was found to be saturable to the concentration of EGF, and was able to be fully suppressed by a specific and potent EGFR tyrosine kinase inhibitor, AG1478. The effect of various known inhibitors/drugs on the DMR response of quiescent A431 cells clearly showed that the EGF-induced DMR involves the Ras/mitogen-activated protein (MAP) kinase pathway, and mainly proceeds through MEK. The DMR signatures obtained here offer integrated quantitative and dynamic representation of EGFR activation and can be used to screen modulators that can regulate critical targets in both the upstream and the downstream EGFR signaling pathways