Single-cell topographical profiling of the immune synapse reveals a biomechanical signature of cytotoxicity.
Sci Immunol
; 9(96): eadj2898, 2024 Jun 28.
Article
em En
| MEDLINE
| ID: mdl-38941478
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sinapses Imunológicas
/
Análise de Célula Única
Limite:
Animals
Idioma:
En
Revista:
Sci Immunol
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos