Macromolecular crowding: an important but neglected aspect of the intracellular environment

Biological macromolecules have evolved over billions of years to function i nside cells, so it is not surprising that researchers studying the properti es of such molecules, either in extracts or in purified form, take care to control factors that reflect the intracellular environment, such as pH, ion ic strength and composition, redox potential and the concentrations of rele vant metabolites and effector molecules. There is one universal aspect of t he cellular interior, however, that is largely neglected - the fact that it is highly crowded with macromolecules. It is proposed that the addition of crowding agents should become as routine as controlling pH and ionic stren gth if we are to meet the objective of studying biological molecules under more physiologically relevant conditions.