Effects of Macromolecular Crowding on Biochemical Systems

Living cells are crowded. The presence of so many macromolecules packed into a confined environment affects the structure and function of biological components, and the kinetics and thermodynamics of biochemical reactions. In fact, crowding studies have already led to important biological insights, such as the existence of metabolons and other temporary protein complexes that play essential roles in metabolism, cell signaling, and organization of the intracellular environment. Even so, this important topic is rarely addressed in chemistry and biochemistry curricula. This review brings readers up to date on developments in the field of macromolecular crowding, with a special emphasis on distinguishing between the two major components of crowding: excluded volume effects (hard interactions) and chemical effects (soft interactions). Interestingly, because attractive soft interactions and repulsive hard interactions oppose each other, the net effects of crowding in vivo are often surprisingly small. We present some background and theory, while summarizing recent literature. Finally, we include suggestions on how this topic might be incorporated into the biochemistry classroom or laboratory setting.