Single-cell topographical profiling of the immune synapse reveals a biomechanical signature of cytotoxicity Journal Article
| Authors: | de Jesus, M.; Settle, A. H.; Vorselen, D.; Gaetjens, T. K.; Galiano, M.; Romin, Y.; Lee, E.; Wong, Y. Y.; Fu, T. M.; Santosa, E.; Winer, B. Y.; Tamzalit, F.; Wang, M. S.; Santella, A.; Bao, Z.; Sun, J. C.; Shah, P.; Theriot, J. A.; Abel, S. M.; Huse, M. |
| Article Title: | Single-cell topographical profiling of the immune synapse reveals a biomechanical signature of cytotoxicity |
| Abstract: | Immune cells have intensely physical lifestyles characterized by structural plasticity and force exertion. To investigate whether specific immune functions require stereotyped mechanical outputs, we used super-resolution traction force microscopy to compare the immune synapses formed by cytotoxic T cells with contacts formed by other T cell subsets and by macrophages. T cell synapses were globally compressive, which was fundamentally different from the pulling and pinching associated with macrophage phagocytosis. Spectral decomposition of force exertion patterns from each cell type linked cytotoxicity to compressive strength, local protrusiveness, and the induction of complex, asymmetric topography. These features were validated as cytotoxic drivers by genetic disruption of cytoskeletal regulators, live imaging of synaptic secretion, and in silico analysis of interfacial distortion. Synapse architecture and force exertion were sensitive to target stiffness and size, suggesting that the mechanical potentiation of killing is biophysically adaptive. We conclude that cellular cytotoxicity and, by implication, other effector responses are supported by specialized patterns of efferent force. |
| Keywords: | mouse; animal; animals; mice; mice, inbred c57bl; c57bl mouse; immunology; cytotoxic t lymphocyte; t-lymphocytes, cytotoxic; cytotoxicity, immunologic; macrophage; macrophages; immunological synapses; immunological synapse; single cell analysis; single-cell analysis; biomechanics; immunocytotoxicity; biomechanical phenomena |
| Journal Title: | Science Immunology |
| Volume: | 9 |
| Issue: | 96 |
| ISSN: | 2470-9468 |
| Publisher: | Amer Assoc Advancement Science |
| Date Published: | 2024-06-01 |
| Start Page: | eadj2898 |
| Language: | English |
| DOI: | 10.1126/sciimmunol.adj2898 |
| PUBMED: | 38941478 |
| PROVIDER: | scopus |
| PMCID: | PMC11826491 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Morgan Huse -- Source: Scopus |
