Abstract
Calcium signaling and tissue nematic order have emerged as key drivers of global cellular behaviors. We first demonstrate that calcium wave propagation is strongly influenced by nematic alignment, with waves traveling faster across tissues when cells are oriented perpendicular to the direction of perturbation. We further show that gap junctions are critical for signal progression, with higher densities along lateral cell edges correlating with increased wave speeds. Combining our experimental results with a reaction–diffusion model, we quantitatively describe calcium wave dynamics across tissues and near topological defects. We then highlight several exciting new directions of this work, including how multinucleated syncytia within the tissue deform the wavefront, as waves propagate faster within syncytia than in mononucleate cells. Finally, we introduce a polymer–gelatin fluorescent biosensor capable of detecting protease secretion from cancer cells, providing a dynamic readout of signaling relevant to cancer progression and metastasis. Together, these findings reveal how tissue microstructure shapes cellular signaling and highlight approaches for developing biosensors that could inform the study and treatment of disease.