text: Macromolecular crowding is an important effect in biochemistry and cell biology. For example, the increase in the strength of interactions between proteins and DNA produced by crowding may be of key importance in processes such as transcription and DNA replication. 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.
  The importance of crowding in protein folding is of particular interest in biophysics. Here, the crowding effect can accelerate the folding process, since a compact folded protein will occupy less volume than an unfolded protein chain. However, crowding can reduce the yield of correctly folded protein by increasing protein aggregation. Crowding may also increase the effectiveness of chaperone proteins such as GroEL in the cell, which could counteract this reduction in folding efficiency. It has also been shown that  macromolecular crowding affects protein-folding dynamics as well as overall protein shape where distinct conformational changes are accompanied by secondary structure alterations implying that crowding-induced shape changes may be important for protein function and malfunction in vivo.
  A particularly striking example of the importance of crowding effects involves the crystallins that fill the interior of the lens. These proteins have to remain stable and in solution for the lens to be transparent; precipitation or aggregation of crystallins causes cataracts. Crystallins are present in the lens at extremely high concentrations, over 500 mg/ml, and at these levels crowding effects are very strong. The large crowding effect adds to the thermal stability of the crystallins, increasing their resistance to denaturation. This effect may partly explain the extraordinary resistance shown by the lens to damage caused by high temperatures.
  Crowding may also play a role in diseases that involve protein aggregation, such as sickle cell anemia where mutant hemoglobin forms aggregates and alzheimer's disease, where tau protein forms neurofibrillary tangles under crowded conditions within neurons.