Macromolecular crowding

The phenomenon of macromolecular crowding alters the properties of molecules in a solution when high concentrations of macromolecules such as proteins are present.

[4] Consequently, measurements of the properties of enzymes or processes in metabolism that are made in the laboratory (in vitro) in dilute solutions may be different by many orders of magnitude from the true values seen in living cells (in vivo).

[8] Added to this mix are various forms of RNA and the cell's DNA chromosome, giving a total concentration of macromolecules of between 300 and 400 mg/ml.

[3] 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.

[10] 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.

[12][13] Crowding has also been suggested to be involved in processes as diverse as the aggregation of hemoglobin in sickle-cell disease, and the responses of cells to changes in their volume.

[21] This effect may partly explain the extraordinary resistance shown by the lens to damage caused by high temperatures.

[4][23] Due to macromolecular crowding, enzyme assays and biophysical measurements performed in dilute solution may fail to reflect the actual process and its kinetics taking place in the cytosol.

[2] Consequently, crowding effects are mimicked in vitro by adding high concentrations of relatively inert molecules such as polyethylene glycol, ficoll, dextran, or serum albumin to experimental media.

Macromolecular crowding in the cytosol of cells alters the properties of macromolecules such as proteins and nucleic acids . [ 1 ]
The volume of accessible solvent (red) for two molecules of widely different sizes (black circles) at high concentrations of macromolecules (grey circles). Reducing the available volume increases the effective concentration of macromolecules.