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

32 Citations (Scopus)

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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Lymphocyte Function-Associated Antigen-1
T-cells
T-Cell Antigen Receptor
Mechanics
Cytoskeleton
Actins
Ligands
T-Lymphocytes
Antigen-Presenting Cells
Immunological Synapses
Cell signaling
Actomyosin
Viral Tumor Antigens
Myosins
Integrins
Polymerization
Adhesion
Chemical activation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

Cite this

Micropatterning of TCR and LFA-1 ligands reveals complementary effects on cytoskeleton mechanics in T cells. / Tabdanov, Erdem; Gondarenko, Sasha; Kumari, Sudha; Liapis, Anastasia; Dustin, Michael L.; Sheetz, Michael; Kam, Lance C.; Iskratsch, Thomas.

In: Integrative Biology (United Kingdom), Vol. 7, No. 10, 01.10.2015, p. 1272-1284.

Research output: Contribution to journalArticle

Tabdanov, E, Gondarenko, S, Kumari, S, Liapis, A, Dustin, ML, Sheetz, M, Kam, LC & Iskratsch, T 2015, 'Micropatterning of TCR and LFA-1 ligands reveals complementary effects on cytoskeleton mechanics in T cells', Integrative Biology (United Kingdom), vol. 7, no. 10, pp. 1272-1284. https://doi.org/10.1039/c5ib00032g
Tabdanov, Erdem ; Gondarenko, Sasha ; Kumari, Sudha ; Liapis, Anastasia ; Dustin, Michael L. ; Sheetz, Michael ; Kam, Lance C. ; Iskratsch, Thomas. / Micropatterning of TCR and LFA-1 ligands reveals complementary effects on cytoskeleton mechanics in T cells. In: Integrative Biology (United Kingdom). 2015 ; Vol. 7, No. 10. pp. 1272-1284.
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