Single-molecule biophysics in signaling: Functionality from stochastic effects

The growing ease with which single molecules can be visualized in living systems is providing a fantastic new view into the molecular processes of cellular signal transduction. The single-molecule perspective reveals stochastic variation and molecular heterogeneity in unaveraged detail and is revealing new mechanisms by which biological functionality is physically achieved. Here we discuss several examples of newly emerging signaling mechanisms intrinsically rooted in the stochastic realm. The common theme is a competitive enzymatic reaction cycle with the substrate and product localized to the membrane, while the controlling enzymes reside in the cytosol. This general reaction configuration is extremely common among signaling systems, and some quite unexpected behaviors can be observed when the functional system includes only a small number of molecules.