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Cell. 2016 Mar 24;165(1):100-110. doi: 10.1016/j.cell.2016.01.021. Epub 2016 Feb 25.

Cytotoxic T Cells Use Mechanical Force to Potentiate Target Cell Killing.

Author information

1
Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
2
Biochemistry and Molecular Biology Graduate Program, Weill-Cornell Medical College, New York, NY 10065, USA.
3
Hydrodynamics Laboratory (LadHyX), Department of Mechanics, Ecole Polytechnique, Palaiseau 91128, France.
4
Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA.
5
Computational Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
6
Program in Cellular and Molecular Medicine, Harvard Medical School, Boston, MA 02115, USA.
7
CNRS, University of Bordeaux, Interdisciplinary Institute for Neuroscience, UMR 5297, Bordeaux 33000, France.
8
Institute Curie, INSERM U932, PSL Research University, Paris 75005, France.
9
Department of Biology, Brooklyn College of the City University of New York, New York, NY 11201, USA.
10
Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. Electronic address: husem@mskcc.org.

Abstract

The immunological synapse formed between a cytotoxic T lymphocyte (CTL) and an infected or transformed target cell is a physically active structure capable of exerting mechanical force. Here, we investigated whether synaptic forces promote the destruction of target cells. CTLs kill by secreting toxic proteases and the pore forming protein perforin into the synapse. Biophysical experiments revealed a striking correlation between the magnitude of force exertion across the synapse and the speed of perforin pore formation on the target cell, implying that force potentiates cytotoxicity by enhancing perforin activity. Consistent with this interpretation, we found that increasing target cell tension augmented pore formation by perforin and killing by CTLs. Our data also indicate that CTLs coordinate perforin release and force exertion in space and time. These results reveal an unappreciated physical dimension to lymphocyte function and demonstrate that cells use mechanical forces to control the activity of outgoing chemical signals.

PMID:
26924577
PMCID:
PMC4808403
DOI:
10.1016/j.cell.2016.01.021
[Indexed for MEDLINE]
Free PMC Article

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