Research over the last two decades has provided compelling evidence that the physical principle of molecular spatiotemporal organization orchestrates information flow at the cell surface. In particular, clustering has emerged as an ubiquitous organizational principle across a myriad of different receptors that bind to distinct ligands, expressed in many cell types and performing different functions [1, 2, 3, 4]. What are the fundamental principles that govern receptor nanoclustering? How are nanoclusters assembled (and dissembled)? What is their role? How are they regulated with such a high fidelity and universality? Here, we provide a vision, based on current literature and our own findings, that addresses these questions.

Nanoclusters can take several forms, typically governed by the mechanism of their construction (see Box 1) and location. Here, we focus on nanoclusters that engage in information flow in the form of chemical and mechanical signals received at the cell surface. These signals are sensed and processed at the plasma membrane where information is then conveyed to the intracellular environment via different signaling cascades for appropriate cell responses.