Cytotoxic T cells use mechanical force to potentiate target cell killing Journal Article
| Authors: | Basu, R.; Whitlock, B. M.; Husson, J.; Le Floc'h, A.; Jin, W.; Oyler-Yaniv, A.; Dotiwala, F.; Giannone, G.; Hivroz, C.; Biais, N.; Lieberman, J.; Kam, L. C.; Huse, M. |
| Article Title: | Cytotoxic T cells use mechanical force to potentiate target cell killing |
| 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. © 2016 Elsevier Inc. |
| Keywords: | signal transduction; controlled study; cytotoxicity; phosphatidylinositol 3 kinase; correlation analysis; cytotoxic t lymphocyte; perforin; cytolysis; target cell; proteinase; protein structure; cell communication; enzyme release; lymphocyte function; immunological synapse; channel gating; target cell destruction; priority journal; article; pore forming cytotoxic protein |
| Journal Title: | Cell |
| Volume: | 165 |
| Issue: | 1 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2016-03-24 |
| Start Page: | 100 |
| End Page: | 110 |
| Language: | English |
| DOI: | 10.1016/j.cell.2016.01.021 |
| PROVIDER: | scopus |
| PMCID: | PMC4808403 |
| PUBMED: | 26924577 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 August 2016 -- Source: Scopus |
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