Effective molarity redux: Proximity as a guiding force in chemistry and biology.

The cell interior is a complex and demanding environment. An incredible variety of molecules jockey to identify the correct position-the specific interactions that promote biology that are hidden among countless unproductive options. Ensuring that the business of the cell is successful requires sophisticated mechanisms to impose temporal and spatial specificity-both on transient interactions and their eventual outcomes. Two strategies employed to regulate macromolecular interactions in a cellular context are co-localization and compartmentalization. Macromolecular interactions can be promoted and specified by localizing the partners within the same subcellular compartment, or by holding them in proximity through covalent or non-covalent interactions with proteins, lipids, or DNA- themes that are familiar to any biologist. The net result of these strategies is an increase in effective molarity: the local concentration of a reactive molecule near its reaction partners. We will focus on this general mechanism, employed by Nature and adapted in the lab, which allows delicate control in complex environments: the power of proximity to accelerate, guide, or otherwise influence the reactivity of signaling proteins and the information that they encode.