Macromolecular crowding as a cell volume sensor

The non-ideal properties of solutions containing high concentrations of mac romolecules can result in enormous increases in the activity of the individ ual macromolecules. There is considerable evidence that macromolecular crow ding and confinement not only occur in cells, but that these are major dete rminants of the activity of the proteins and other intracellular macromolec ules. This concept has important implications for cell volume regulation be cause, under crowded conditions, relatively small changes in concentration, consequent to alterations of water content, lead to large changes in macro molecular activity which could provide a mechanism by which cells sense cha nges in their volume. This brief review considers 1) direct demonstrations that introducing a high concentration of appropriate macromolecules into ce lls in vitro produced volume regulatory changes, 2) the physical chemical p rinciples involved in the effects of crowding of macromolecules on their ac tivity, 3) estimates of the actual intracellular activity of macromolecules , 4) a proposed model of how changes in macromolecular crowding could signa l volume regulation in cells, and 5) brief consideration of the complexitie s introduced by interactions between macromolecules, water and cosolutes. C onclusions: The hypothesis that macromolecular crowding provides a mechanis m by which cells sense changes in their volume is plausible and is supporte d by striking observations in red blood cell ghosts and perfused barnacle m uscle cells. However, the signaling molecules involved have not been identi fied, the proposed model is not fully consistent with the experiments, expe rimental verification in intact cells is lacking, and numerous alternative or additional mechanisms are not excluded. Copyright (C) 2000 S. Karger AG, Basel.