Micropatterning of TCR and LFA-1 ligands reveals complementary effects on cytoskeleton mechanics in T cells

Erdem Tabdanov, Sasha Gondarenko, Sudha Kumari, Anastasia Liapis, Michael L. Dustin, Michael Sheetz, Lance C. Kam, Thomas Iskratsch

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

The formation of the immunological synapse between a T cell and the antigen-presenting cell (APC) is critically dependent on actin dynamics, downstream of T cell receptor (TCR) and integrin (LFA-1) signalling. There is also accumulating evidence that mechanical forces, generated by actin polymerization and/or myosin contractility regulate T cell signalling. Because both receptor pathways are intertwined, their contributions towards the cytoskeletal organization remain elusive. Here, we identify the specific roles of TCR and LFA-1 by using a combination of micropatterning to spatially separate signalling systems and nanopillar arrays for high-precision analysis of cellular forces. We identify that Arp2/3 acts downstream of TCRs to nucleate dense actin foci but propagation of the network requires LFA-1 and the formin FHOD1. LFA-1 adhesion enhances actomyosin forces, which in turn modulate actin assembly downstream of the TCR. Together our data shows a mechanically cooperative system through which ligands presented by an APC modulate T cell activation.

Original languageEnglish (US)
Pages (from-to)1272-1284
Number of pages13
JournalIntegrative Biology (United Kingdom)
Volume7
Issue number10
DOIs
StatePublished - Oct 1 2015
Externally publishedYes

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ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

Cite this

Tabdanov, E., Gondarenko, S., Kumari, S., Liapis, A., Dustin, M. L., Sheetz, M., Kam, L. C., & Iskratsch, T. (2015). Micropatterning of TCR and LFA-1 ligands reveals complementary effects on cytoskeleton mechanics in T cells. Integrative Biology (United Kingdom), 7(10), 1272-1284. https://doi.org/10.1039/c5ib00032g