EAGER: Quantum Imaging for Precise Mapping of Protein Organization during Signaling

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Cells have proteins called receptors that bind to signaling molecules and initiate a physiological response. Receptors are generally transmembrane proteins, which bind to signaling molecules outside the cell and subsequently transmit the signal through a sequence of molecular switches to internal signaling pathways. Currently, there are no reliable methods to determine both stoichiometry and precise distances between proteins in a signaling cluster, which is critical for understanding the fundamental mechanisms that control signaling. Quantum-enhanced measurements proposed in this project will allow to approach the physical limits in precision to study protein-protein interactions and determine protein organization during cellular signaling. Undergraduate and graduate students involved in the project will acquire experience in diverse areas including fluorescence microscopy, quantum optics and precision measurements, single-photon detection technologies, cell signaling, and biology.This project will demonstrate quantum-enhanced measurements to realize ultra-precise characterization of protein-protein interactions in intact cells. An image inversion interferometer system for two-point source imaging with high precision will be constructed, and a fast feedback system for center of mass positioning required for the Quantum Imaging technique will be developed. Analyses and estimators that integrate distance measurements and traditional single molecule super resolution microscopy (SMSR) information will be applied to study EGFR and EGFR/Ron clusters on the membrane of intact cells. The proposed work will develop a novel technology that merges quantum-enhanced imaging techniques with state-of-the art SMSR, to provide a 10-fold resolution enhancement for precise imaging of proteins in signaling clusters with approximately 1 nm resolution. This project is supported by the Biological Sciences Directorate.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.