Cellular Mechanics and Interactions
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It is concluded that cellular cytotoxicity and, by implication, other effector responses are supported by specialized patterns of efferent force, which demonstrate that immune cells exert specialized patterns of force on their targets to carry out distinct immunological functions.
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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.
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@article{Jesus2024Single,
title = {Single-cell topographical profiling of the immune synapse reveals a biomechanical signature of cytotoxicity},
author = {Miguel de Jesus and Alexander Settle and Daan Vorselen and Thomas K. Gaetjens and Michael Galiano and Yevgeniy Romin and E. Hui Clarissa Lee and Yung Yu Wong and Tian-Ming Fu and Endi K. Santosa and Benjamin Y. Winer and Fella Tamzalit and Mitchell S. Wang and Anthony Santella and Zhirong Bao and Joseph C. Sun and Pavak K. Shah and Julie A. Theriot and Steven M. Abel and Morgan Huse},
journal = {Science Immunology},
year = {2024},
doi = {10.1126/sciimmunol.adj2898},
url = {https://doi.org/10.1126/sciimmunol.adj2898}
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