Brownian Models of Chemical Reactions in Microdomains

Biological microstructures such as synapses, dendritic spines, subcellular domains, sensor cells, and many other structures are regulated by chemical reactions that involve only a small number of molecules, that is, between a few and up to thousands of molecules. Traditional chemical kinetics theory may provide an inadequate description of chemical reactions in such microdomains. Models with a small number of diffusers can be used to describe noise due to gating of ionic channels by random binding and unbinding of ligands in biological sensor cells, such as olfactory cilia, photoreceptors, and hair cells in the cochlea. A chemical reaction that involves only 10–100 proteins can cause a qualitative transition in the physiological behavior of a given part of a cell. Large fluctuations should be expected in a reaction if so few molecules are involved, both in transient and persistent binding and unbinding reactions. In the latter case, large fluctuations in the number of bound molecules can force the physiological state to change all the time, unless there is a specific mechanism that prevents the switch and stabilizes the physiological state. Therefore, a theory of chemical kinetics of such reactions is needed to predict the threshold at which switches occur and to explain how the physiological function is regulated in molecular terms at a subcellular level.