Macromolecular crowding and its potential impact on nuclear function

It is well established, that biochemical reactions are dependent on pH, ionic strength, temperature and the concentration of reactants. However, the steric repulsion among bulky components of biological systems also affect biochemical behavior: The ‘excluded volume effect of macromolecular crowding’ drives bulky components into structurally compact organizations, increases their thermodynamic activities and slows down diffusion. The very special composition of the cell nucleus, which is packed with high-molecular chromatin, ribonucleo-particles and associated proteins, suggests that crowding-effects are part of nuclear functionality. Realizing that many nuclear processes, notably gene transcription, hnRNA splicing and DNA replication, use macromolecular machines, and taking into account that macromolecular crowding provides a cooperative momentum for the assembly of macromolecular complexes, we here elaborate why macromolecular crowding may be functionally important in supporting the statistical significance of nuclear activities.