T Cell Receptor Co-Stimulation Through Magnetogenetic Tools: A Platform for Wireless Rewiring of Cellular Signaling

Synthetic biology offers innovative strategies to control cell function for therapeutic applications. Here, we present a magnetogenetic platform for T cell receptor (TCR) costimulation using magnetic fields to achieve noninvasive activation of T cells. We employed engineered TRPV1, TRPV4, and electromagnetic perceptive gene (EPG) constructs in HEK293, Jurkat, and primary human T cells. Calcium imaging confirmed functional activation of these tools, while qPCR and proteomic analyses revealed downstream effects on activation markers, calcium signaling, mitochondrial function, and membrane integrity. In Jurkat and primary T cells, magnetic stimulation alone reduced activation signatures, but when combined with antigenic stimulation, it significantly enhanced T cell activation. This dual-modality response indicates that magnetogenetic tools can serve as tunable costimulators of TCR signaling. Our findings highlight the potential of wireless, magnetically controlled systems to precisely modulate immune cell behavior, with implications for the development of next-generation cell-based immunotherapies.