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4D electron microscopy of T cell activation

Lu, Yue and Yoo, Byung-Kuk and Ng, Alphonsus H. C. and Kim, Jungwoo and Yeom, Sinchul and Tang, Jau and Lin, Milo M. and Zewail, Ahmed H. and Heath, James R. (2019) 4D electron microscopy of T cell activation. Proceedings of the National Academy of Sciences of the United States of America, 116 (44). pp. 22014-22019. ISSN 0027-8424. PMCID PMC6825259. https://resolver.caltech.edu/CaltechAUTHORS:20191015-074715875

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Abstract

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 stimulation-induced 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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1073/pnas.1914078116DOIArticle
https://www.pnas.org/content/suppl/2019/10/08/1914078116.DCSupplementalPublisherSupporting Information
http://www.ncbi.nlm.nih.gov/pmc/articles/pmc6825259/PubMed CentralArticle
ORCID:
AuthorORCID
Lu, Yue0000-0001-9036-2803
Yoo, Byung-Kuk0000-0002-2610-6685
Ng, Alphonsus H. C.0000-0003-0074-4598
Kim, Jungwoo0000-0002-5215-2044
Yeom, Sinchul0000-0001-6449-0844
Tang, Jau0000-0003-2078-1513
Lin, Milo M.0000-0001-8680-2685
Heath, James R.0000-0001-5356-4385
Additional Information:© 2019 National Academy of Sciences. Published under the PNAS license. Edited by Pamela J. Bjorkman, California Institute of Technology, Pasadena, CA, and approved September 22, 2019 (received for review August 15, 2019). PNAS first published October 14, 2019. We thank D. Baltimore for providing MART-1-specific Jurkat cells and K. A. Woodrow for providing the Zetasizer. Funding: This work was supported by the National Cancer Institute of the National Institutes of Health (U01CA217655). The authors thank the Parker Institute for Cancer Immunotherapy (PICI) for support. A.H.C.N. is supported by a Banting Postdoctoral Fellowship from the Government of Canada. M.M.L. acknowledges the Welch Foundation for support. Author contributions: Y.L., B.-K.Y., A.H.C.N., J.K., J.T., A.H.Z., and J.R.H. designed research; Y.L., B.-K.Y., A.H.C.N., and J.K. performed research; Y.L., B.-K.Y., A.H.C.N., S.Y., and A.H.Z. contributed new reagents/analytic tools; Y.L., B.-K.Y., A.H.C.N., S.Y., J.T., M.M.L., and J.R.H. analyzed data; and Y.L., B.-K.Y., A.H.C.N., and J.R.H. wrote the paper. The authors declare no competing interest. This article is a PNAS Direct Submission. This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1914078116/-/DCSupplemental.
Funders:
Funding AgencyGrant Number
NIHU01CA217655
National Cancer InstituteUNSPECIFIED
Natural Sciences and Engineering Research Council of Canada (NSERC)UNSPECIFIED
Robert A. Welch FoundationUNSPECIFIED
Subject Keywords:T cell activation; PINEM; electron microscopy; electron-photon coupling; T cell receptor
Issue or Number:44
PubMed Central ID:PMC6825259
Record Number:CaltechAUTHORS:20191015-074715875
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20191015-074715875
Official Citation: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. Proceedings of the National Academy of Sciences Oct 2019, 116 (44) 22014-22019; DOI: 10.1073/pnas.1914078116.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:99266
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:15 Oct 2019 15:01
Last Modified:02 Jun 2020 18:39

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