MACROMOLECULAR CROWDING AND CONFINEMENT IN CELLS EXPOSED TO HYPERTONICITY

The nonideal properties of solutions containing high concentrations of macromolecules can result in enormous increases in the activity of th e individual macromolecules. It has been proposed that molecular crowd ing and confinement occur in cells and are major determinants of the a ctivity of the proteins and other intracellular macromolecules. This c oncept has important implications for cell volume regulation because, under crowded conditions, relatively small changes in concentration, c onsequent to alterations of water content, lead to large changes in ma cromolecular activity. This review considers several aspects of macrom olecular crowding and confinement, including: 1) the physical chemical principles involved; 2) in vitro demonstrations of the effects; 3) re lation to water activity; 4) estimates of the actual intracellular act ivity of water and macromolecules; 5) relation to osmotic regulation i n various types of cells, including bacteria, red blood cells, and com plex nucleated cells; and 6) the relation to inorganic ions and organi c osmolytes in cells stressed by hypertonicity. We conclude that, whil e there is compelling evidence for important effects of molecular crow ding in vitro and in red blood cells, the role of macromolecular crowd ing and confinement in osmotic regulation of more complex cells is an open question that deserves the extensive attention it is currently re ceiving.