Chemical and synthetic biology tools to interrogate and control cell–cell interactions in vivo

Cell-cell interactions are fundamental to multicellular organisms, governing development, maintaining tissue homeostasis, and enabling responses to perturbations. Accordingly, the development of effective tools to investigate cell-cell communication in its native context is essential for addressing fundamental biological questions. In recent years, substantial progress has been made toward studying these processes directly in vivo, where cellular dynamics, tissue architecture, and environmental cues are preserved. This review discusses these in vivo advances, focusing on how chemical and synthetic biology tools enable the interrogation and control of cell- and protein-mediated communication in living organisms. We discuss the evolution of these technologies and illustrate how they are being applied to uncover general principles of cellular interaction within complex biological systems.