Macromolecular crowding and its role as intracellular signalling of cell volume regulation

Macromolecular crowding has been proposed as a mechanism by means of which a cell can sense relatively small changes in volume or, more accurately, the concentration of intracellular solutes. According to the macromolecular theory, the kinetics and equilibria of enzymes can be greatly influenced by small changes in the concentration of ambient, inert macromolecules. A 10% change in the concentration of intracellular proteins can lead to changes of up to a factor of ten in the thermodynamic activity of putative molecular regulatory species, and consequently, the extent to which such regulator(s) may bind to and activate membrane-associated ion transporters. The aim of this review is to examine the concept of macromolecular crowding and how it profoundly affects macromolecular association in an intact cell with particular emphasis on its implication as a sensor and a mechanism through which cell volume is regulated.