How can biochemical reactions within cells differ from those in test tubes?

Abstract

Nonspecific interactions between individual macro-molecules and their immediate surroundings (`background interactions') within a medium as heterogeneous and highly volume occupied as the interior of a living cell can greatly influence the equilibria and rates of reactions in which they participate. Background interactions may be either repulsive, leading to preferential size-and-shape-dependent exclusion from highly volume-occupied elements of volume, or attractive, leading to nonspecific associations or adsorption. Nonspecific interactions with different constituents of the cellular interior lead to three classes of phenomena: macromolecular crowding, confinement and adsorption. Theory and experiment have established that predominantly repulsive background interactions tend to enhance the rate and extent of macromolecular associations in solution, whereas predominately attractive background interactions tend to enhance the tendency of macromolecules to associate on adsorbing surfaces. Greater than order-of-magnitude increases in association rate and equilibrium constants attributable to background interactions have been observed in simulated and actual intracellular environments.