The influence of macromolecular crowding on thermodynamic activity: solubility and dimerization constants for...

Macromolecules in solution can have large effects on the properties of other solutes through nonideal excluded-volume (crowding) interactions. Minton has calculated such effects by treating the macromolecules as a hard-sphere fluid in a background of an inert structureless solvent. In the present paper these calculations are extended by including the primary solvent as a separate component in a hard-sphere mixture. The results are in good agreement with experimental data. However, some predictions of this model differ drastically from those based on Minton's approach. Thus, much smaller effects from macromolecular crowding, particularly by smaller molecules, are expected. The present results also predict a much larger dependence on the shape of the molecules under study; notably for a dimerization reaction, it is found that the excluded-volume effects actually can destabilize side-by-side binding of two spherical molecules, while a dimerization to a spherical complex is stabilized. Therefore there will exist intermediate shapes of complexes whose stability is insensitive to crowded-volume effects. The consequences for crowding effects inside the living cell are also discussed.