4D electron microscopy of T cell activation

Yue Lu, Byung Kuk Yoo, Alphonsus H.C. Ng, Jungwoo Kim, Sinchul Yeom, Jau Tang, Milo M. Lin, Ahmed H. Zewail, James R. Heath

Research output: Contribution to journalArticle


T cells can be controllably stimulated through antigen-specific or nonspecific protocols. Accompanying functional hallmarks of T cell activation can include cytoskeletal reorganization, cell size increase, and cytokine secretion. Photon-induced near-field electron microscopy (PINEM) is used to image and quantify evanescent electric fields at the surface of T cells as a function of various stimulation conditions. While PINEM signal strength scales with multiple of the biophysical changes associated with T cell functional activation, it mostly strongly correlates with antigen-engagement of the T cell receptors, even under conditions that do not lead to functional T cell activation. PINEM image analysis suggests that a stimulationinduced reorganization of T cell surface structure, especially over length scales of a few hundred nanometers, is the dominant contributor to these PINEM signal changes. These experiments reveal that PINEM can provide a sensitive label-free probe of nanoscale cellular surface structures.

Original languageEnglish (US)
Pages (from-to)22014-22019
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number44
StatePublished - Oct 29 2019


  • Electron microscopy
  • Electron-photon coupling
  • T cell activation
  • T cell receptor

ASJC Scopus subject areas

  • General

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  • Cite this

    Lu, Y., Yoo, B. K., Ng, A. H. C., Kim, J., Yeom, S., Tang, J., Lin, M. M., Zewail, A. H., & Heath, J. R. (2019). 4D electron microscopy of T cell activation. Proceedings of the National Academy of Sciences of the United States of America, 116(44), 22014-22019. https://doi.org/10.1073/pnas.1914078116