New perspectives of mechanobiology are emerging in the biomedical sciences. Recent evidence indicates that immune cells regulate their cell mechanics not only  downstream of signalling events triggered by ligand–receptor binding, but that cells employ a diversity of feedback mechanisms to dynamically adjust their mechanics in response to external stimuli. Quantifying cellular forces has therefore become an contentious challenge across multiple disciplines at the interface of biophysics and immunology. Mechanical forces are especially important for the activation of immune T cells. Applying sensitive quantitative super-resolution imaging and force probing methodologies to analyse resting and activated T cells, we demonstrate that the kinetics of the antigen engaging the T-cell receptor controls the nanoscale actin organisation and mechanics of the IS. Using an engineered T-cell system expressing a specific T-cell receptor and stimulated by a range of antigens, force measurements revealed that the peak force experienced by the T-cell receptor during activation was independent of the kinetics of the stimulating antigen. Conversely, quantification of the actin retrograde flow velocity at the IS revealed a striking dependence on the antigen kinetics. Consequently, tuning actin dynamics in response to antigen kinetics may thus be a mechanism that allows T cells to adjust the length- and time-scale of T-cell receptor signalling. Harvesting these insights into mechanobiology of T cells, we engineer synthetic antigen presenting cells to control T-cell differentiation. Novel ultra-thin superextended lightsheet technology allow to correlate early calcium activation signalling, IS formation, and effector T-cell function across scales. Taken together, the Biophysical Immunology Laboratory now democratises the established technologies with the microscopy company ZEISS in the Oxford-ZEISS Centre of Excellence.

15:15: Coffee Break

15:30: Nils Piernitzki (AG Staufer), Bottom-up assembly of an artificial tumor immuno-microenvironment 

 15:45: Xiangda Zhou (A2, AG Qu), Synthetic T Cells Functionalized with IL-2 Enhance NK Cell Cytotoxicity Mimicking CD4+ T Cells

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