Decoding mechanoregulation in immunological synapses using biomimetic artificial cells

Mechanical force-driven signaling has emerged as a key regulator of cell-cell interactions (CCIs), which can enhance immune cell function. However, current biochemical approaches for studying CCIs offer minimal direct control over cellular bulk phenotypes, while synthetic biomaterial systems fail to mimic the dynamic complexity of cells. Here we introduce kpiCells, a biomaterial-based platform that uses a biomimetic membrane-endoplasmic architecture to enable finely tuned phenocopying of cellular states via modular mechanical, chemical and topographical inputs. We demonstrate that kpiCells can engage in physiological CCIs and reproduce critical subcellular features. In T cell systems, kpiCells enable integrated interrogation of afferent mechanosensing pathways and efferent force-exertion pathways, and support measurement of piconewton-scale forces at individual T cell antigen receptors as well as single cell-cell force fingerprints that define activation thresholds. This work establishes kpiCells as a bionic model that enables synthetic material design with the level of functional complexity approaching living cell systems.