Know the Single-Receptor Sensing Limit? Think Again

How cells reliably infer information about their environment is a fundamentally important question. While sensing and signaling generally start with cell-surface receptors, the degree of accuracy with which a cell can measure external ligand concentration with even the simplest device—a single receptor—is surprisingly hard to pin down. Recent studies provide conflicting results for the fundamental physical limits. Comparison is made difficult as different studies either suggest different readout mechanisms of the ligand-receptor occupancy, or differ on how ligand diffusion is implemented. Here we critically analyse these studies and present a unifying perspective on the limits of sensing, with wide-ranging biological implications.