Vortragstitel: Synthetic cell-based artificial tissues to study T cell activation
T cells integrate biochemical and biophysical cues within lymph nodes, collectively determining activation of adaptive immunity. Quantitatively understanding how mechanical and biochemical signals converge at the single-cell and tissue level requires new model systems. To address this, we developed millimeter-sized artificial lymph nodes assembled from synthetic cells and artificial extracellular matrix. The mechanical properties of the synthetic cells, specifically their Young’s modulus, can be precisely tuned, while their surfaces can be functionalized with biochemical stimuli. This allows to independently tune their biomechanics and biochemistry. The resulting tissue architecture, including its anisotropy and stiffness, can be engineered to probe emergent, tissue-scale phenomena. Performing live cell microscopy of migrating T-cells within synthetic lymph nodes, we validate that they reproduce in vivo T-cell motility. Statistical modeling of migration trajectories reveals that tissues must support search strategies for effective signal integration and that confinement degree promotes regulatory phenotypes of the T cells. Our synthetic cell-based tissues recapitulate architectural features of lymphatic organs, providing a platform to dissect how mechano-signaling interacts with biochemical cues to shape T-cell immunity.