Figure 4

Macromolecular crowding promotes self-association. When molecules have the ability to self-interact, macromolecular crowding enhances their aggregation. Several situations are presented in the cartoons, two of which are common in cells (panels A and C) i.e. large macromolecules, some of which can self-associate, against a high background of non-interacting molecules. Panel A: large, self-associating macromolecules (red circles) are present alongside a high background of non-interacting molecules (blue circles) big enough to be excluded from the grey area around the big molecules, e.g. proteins or other polymers. When several red molecules self-associate the total exclusion zone decreases (grey area), increasing the area of mobility available to the blue molecules. Therefore by aggregating the red macromolecules the entropy of the system increases. Panel B: under non-crowded conditions there is no restriction on the mobility of the blue or red molecules, aggregation of red molecules results in only a small increase in entropy. Under these condition, aggregation of the red molecules is not favoured [35]. Panel C: large macromolecules present alongside a high concentration of relatively small molecules e.g. salt molecules. Panel D: similar situation to panel C, but with a low concentration of small blue molecules. In both C and D, the small molecules have free access to the entire system. Consequently there is no thermodynamic advantage for the large macromolecules to associate; therefore aggregation of large macromolecules is not affected by the concentration of the small molecules.