NONCONTACT MEMBRANE PROTEIN PROBE

Reading the conformational state of membrane proteins is central to understanding their role in cell signaling, to using them as sensor elements and for screening candidate drug compounds that are targeted toward this important class of biomolecules. While the patch clamp technique for doing this is ubiquitous, it does have significant limitations: two electrodes are required to measure current flow, the GW input impedance combines with unavoidable stray capacitance to limit the amplifier's bandwidth (typically to -10 kHz), and the GW seal required at the cell membrane precludes scanning to image both distribution and dynamics of membrane proteins. To address these limitations, we will develop near-field probes to confine high-frequency excitation to sub-wavelength proportions, enabling interaction with single membrane proteins. Since there are inherent dielectric contrast mechanisms available in protein-lipid systems, these can be used at high frequencies to provide a new method of protein readout. The overall goal of this work is to build scanning protein probes that can image distribution and dynamics of ion channel activity simultaneously.