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Altered Actin Centripetal Retrograde Flow in Physically Restricted Immunological Synapses

Journal Article · · PLoS ONE
 [1];  [2];  [3];  [4];  [5]
  1. National Univ. of Singapore (Singapore). Research Centre of Excellence in Mechanobiology; Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; DOE/OSTI
  2. Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Physical Biosciences and Materials Sciences Divisions
  3. Univ. of California, San Francisco, CA (United States). Dept. of Cellular and Molecular Pharmacology; National Inst. for Materials Science (NIMS), Tsukuba (Japan). Biomaterials Center
  4. Univ. of California, San Francisco, CA (United States). Dept. of Cellular and Molecular Pharmacology; Howard Hughes Medical Inst., Chevy Chase, MD (United States)
  5. National Univ. of Singapore (Singapore). Research Centre of Excellence in Mechanobiology; Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Univ. of California, San Francisco, CA (United States). Dept. of Cellular and Molecular Pharmacology; Howard Hughes Medical Inst., Chevy Chase, MD (United States)
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Antigen recognition by T cells involves large scale spatial reorganization of numerous receptor, adhesion, and costimulatory proteins within the T cell-antigen presenting cell (APC) junction. The resulting patterns can be distinctive, and are collectively known as the immunological synapse. Dynamical assembly of cytoskeletal network is believed to play an important role in driving these assembly processes. In one experimental strategy, the APC is replaced with a synthetic supported membrane. An advantage of this configuration is that solid structures patterned onto the underlying substrate can guide immunological synapse assembly into altered patterns. Here, we use mobile anti-CD3e on the spatial-partitioned supported bilayer to ligate and trigger T cell receptor (TCR) in live Jurkat T cells. Simultaneous tracking of both TCR clusters and GFP-actin speckles reveals their dynamic association and individual flow patterns. Actin retrograde flow directs the inward transport of TCR clusters. Flow-based particle tracking algorithms allow us to investigate the velocity distribution of actin flow field across the whole synapse, and centripetal velocity of actin flow decreases as it moves toward the center of synapse. Localized actin flow analysis reveals that, while there is no influence on actin motion from substrate patterns directly, velocity differences of actin are observed over physically trapped TCR clusters. Actin flow regains its velocity immediately after passing through confined TCR clusters. These observations are consistent with a dynamic and dissipative coupling between TCR clusters and viscoelastic actin network.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1627417
Journal Information:
PLoS ONE, Journal Name: PLoS ONE Journal Issue: 7 Vol. 5; ISSN 1932-6203
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English

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Cited By (21)

Integrin-Matrix Clusters Form Podosome-like Adhesions in the Absence of Traction Forces journal December 2013
F-actin polymerization and retrograde flow drive sustained PLCγ1 signaling during T cell activation journal June 2012
Formin-generated actomyosin arcs propel T cell receptor microcluster movement at the immune synapse journal October 2016
Micro–adhesion rings surrounding TCR microclusters are essential for T cell activation journal July 2016
Contractile actomyosin arcs promote the activation of primary mouse T cells in a ligand-dependent manner journal August 2017
Biophysical Aspects of T Lymphocyte Activation at the Immune Synapse journal February 2016
Action and Traction: Cytoskeletal Control of Receptor Triggering at the Immunological Synapse journal March 2016
Phospholipids: Pulling Back the Actin Curtain for Granule Delivery to the Immune Synapse journal April 2019
Actin foci facilitate activation of the phospholipase C-γ in primary T lymphocytes via the WASP pathway journal March 2015
Early integrin binding to Arg-Gly-Asp peptide activates actin polymerization and contractile movement that stimulates outward translocation journal December 2011
CD28 and CD3 have complementary roles in T-cell traction forces journal January 2014
Mechanosensing drives acuity of αβ T-cell recognition journal August 2017
Multiple actin networks coordinate mechanotransduction at the immunological synapse journal January 2020
How cells engulf: a review of theoretical approaches to phagocytosis journal October 2017
Actin retrograde flow and actomyosin II arc contraction drive receptor cluster dynamics at the immunological synapse in Jurkat T cells journal March 2012
A Composition-Dependent Molecular Clutch Between T Cell Signaling Condensates and Actin posted_content October 2018
Mapping the stochastic sequence of individual ligand-receptor binding events to cellular activation: T cells act on the rare events journal January 2019
Actin retrograde flow and actomyosin II arc contraction drive receptor cluster dynamics at the immunological synapse in Jurkat T cells text January 2012
Distinct Roles of Cytoskeletal Components in Immunological Synapse Formation and Directed Secretion journal September 2015
Calcium influx through CRAC channels controls actin organization and dynamics at the immune synapse journal July 2016
A composition-dependent molecular clutch between T cell signaling condensates and actin journal July 2019

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