Cells determine the concentration of signaling molecules (e.g., nutrients or toxins in the environment or intracellular transcription factors) by registering associated receptors as “bound” or “unbound” (the inset shows the receptor “readout” over time). As shown schematically for bacterial chemotaxis, a network of reactions transduces the external signal measured by cell surface receptors into a change in concentration of an intracellular protein, which is in turn measured by receptors at the base of the motor. This measurement biases the motor’s direction of rotation, which controls whether the cell runs or tumbles (changes direction). Cells compare the measurement of their external environment at a given time with their memory of it some time ago, and determine the temporal change. The work by Mora and Wingreen  shows that by monitoring the average unbound interval rather than the average binding occupancy, a biological receptor is able to reduce the uncertainty in the measurement process by a factor of two.