Macromolecular Crowding - Cause and Effects

Cause and Effects

The interior of cells is a crowded environment. For example, an Escherichia coli cell is only about 2 micrometres (μm) long and 0.5 μm in diameter, with a cell volume of 0.6 - 0.7 μm3. However, E. coli can contain up to 4,288 different types of proteins, and about 1,000 of these types are produced at a high enough level to be easily detected. Added to this mix are various forms of RNA and the cell's DNA chromosome, giving a total concentration of macromolecules of between 300 to 400 mg/ml. In eukaryotes the cell's interior is further crowded by the protein filaments that make up the cytoskeleton, this meshwork divides the cytosol into a network of narrow pores.

These high concentrations of macromolecules occupy a large proportion of the volume of the cell, which reduces the volume of solvent that is available for other macromolecules. This excluded volume effect increases the effective concentration of macromolecules (increasing their chemical activity), which in turn alters the rates and equilibrium constants of their reactions. In particular this effect alters dissociation constants by favoring the association of macromolecules, such as when multiple proteins come together to form protein complexes, or when DNA-binding proteins bind to their targets in the genome. Crowding may also affect enzyme reactions involving small molecules if the reaction involves a large change in the shape of the enzyme.

The size of the crowding effect depends on both the molecular mass and shape of the molecule involved, although mass seems to be the major factor – with the effect being stronger with larger molecules. Notably, the size of the effect is non-linear, so macromolecules are much more strongly affected than are small molecules such as amino acids or simple sugars. Macromolecular crowding is therefore an effect exerted by large molecules on the properties of other large molecules.