National Academy of Sciences, Proceedings of the National Academy of Sciences, 44(116), p. 22014-22019, 2019
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Significance Photon-induced near-field electron microscopy (PINEM) enables the visualization of nanoscale structures and interfaces with enhanced contrast due to the energy gain of electrons from light-excited evanescent electromagnetic fields. Here we optimized a PINEM approach to directly image and quantify these fields at the surface of T cells as a function of various stimulation conditions. We found that while PINEM is sensitive to multiple biophysical changes associated with T cell activation, it strongly correlates with binding of specific antigen major histocompatibility complex, even without accompanying functional T cell activation. Our results suggest that PINEM can find use as a cellular imaging tool, with exquisite surface selectivity and high sensitivity to structural changes on the length scale of cell surface protein aggregates.