ABSTRACT
This chapter discusses the macromolecular crowding profoundly affects macromolecular associations in an intact cell. It shows that extremely simple models incorporating principles of macromolecular crowding can account for signal amplification of both swelling-activated and shrinkage-activated ion flux. The maintenance of cell volume in the face of osmotic stress necessitates the existence of a feedback loop containing at least two functional elements: a sensor that detects transient changes in volume, and a sensor-activated effector that operates to restore the original volume. However, even these simplified models are capable of exhibiting activation of transporters via swelling and shrinkage, with signal amplification as great as that observed experimentally. The important lesson to be learned here is that small fractional volume changes of a cell can, via alteration of macromolecular crowding, influence association equilibria and enzyme-catalyzed reaction rates by a far greater extent than expected on the basis of simplistic considerations of mass action.
