T-cell synapses in three-dimensional confinement - Linking biomechanics and bioenergetics

• Applicant: Dr. Anna Schepers
• Subject Area: Biophysics
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 533765530

When immune cells combat cancer, they experience a mechanically challenging, three-dimensional, and spatially confined environment. To mechanically interact with and kill tumour cells, the immune cells need to orchestrate a complex series of morphological changes and biochemical and biomechanical signalling events while they are constantly exposed to the mechanical restrictions of the environment. In the proposed project, we aim to link the energetic cost of the T-cell immune synapse and of the generation of mechanical forces in response to three-dimensional confinement. Using state-of-the-art lattice light sheet fluorescence microscopy, we plan to characterise the mechanical interaction forces between a T cell and a specifically developed synthetic target cell. We will further characterise the T-cell morphology and matrix deformation. We aim to link these observations with the energy supply in the T cell and the changes in model systems with different confinements. Our findings have the potential to open a new perspective on why dense tumours are not effectively targeted by the adaptive immune response.

• DFG Programme: WBP Fellowship
• International Connection: United Kingdom
• Host: Professor Marco Fritzsche, Ph.D.