We examine the impact of intercellular interactions on cellular function. We have used coculture, imaging and perturbation strategies, as well as matched computational methods, to reinforce findings from dissociated samples, validate inferred cell-cell communication in vivo (e.g., between sensory neurons and lymph node resident cells), and manipulate multicellular systems (e.g., organoids). We are currently working on building arrayed, synthetically-designed cellular ensembles to examine how ‘tissue’ structure impacts functional response. Our overall goal is to understand cellular co-dependencies that influence niche- and tissue-level response dynamics.