Engineered Tools to Study Intercellular Communication

All multicellular organisms rely on intercellular communication networks to coordinate physiological functions. As members of a dynamic social network, each cell receives, processes, and redistributes biological information to define and maintain tissue homeostasis. Uncovering the molecular programs underlying these processes is critical for prevention of disease and aging and development of therapeutics. The study of intercellular communication requires techniques that reduce the scale and complexity of in vivo biological networks while resolving the molecular heterogeneity in “omic” layers that contribute to cell state and function. Recent advances in microengineering and high‐throughput genomics offer unprecedented spatiotemporal control over cellular interactions and the ability to study intercellular communication in a high‐throughput and mechanistic manner. Herein, this review discusses how salient engineered approaches and sequencing techniques can be applied to understand collective cell behavior and tissue functions. Understanding how intercellular communication circuits orchestrate complex biological processes is a fundamental goal of cell biology with therapeutic applications. This review discusses recent advances in microengineered and molecular profiling technologies that offer unprecedented access to the molecular machinery governing cell behavior, and how these tools reveal heterogeneity within networks of interacting cells along spatial and temporal axes.