The Influence of Macromolecular Crowding and Macromolecular Confinement on Biochemical Reactions in Physiological Media*

By A. Minton. Journal of Biological Chemistry, 2001

1,303 citations recorded by the source corpus.

Detailed knowledge of the rates, equilibria, and mechanism of biochemical reactions has traditionally been acquired through experiments conducted on solutions containing low concentrations (less than about 1 mg/ml) of total protein, nucleic acid, and/or polysaccharide together with buffer salts, low molecular weight substrates, and cofactors as required. In con-trast, biochemical reactions in living systems take place in media containing substantially greater total concentrations (50–400 mg/ml) of macromolecules that may be present in solution and/or in indefinitely large arrays (e.g. cytoskeletal fibers) (1, 2). Because no single macromolecular species may be present at high concentration, but all species taken together occupy a significant fraction of the volume of the medium, such media are referred to as “crowded” (3) and/or “confining” (4) rather than “concentrated,” depending upon whether the macrosolutes are soluble and/or structured. Fig. 1 provides a sche-matic illustration of crowding and confinement in eukaryotic cytoplasm. In such media, nonspecific interactions between macrosolutes contribute significantly to the total free energy of the medium. High concentrations of “background” macromolecules that do not participate directly in a particular test reaction have been observed to induce order-of-magnitude or greater changes in the rates and equilibria of numerous test reactions (see below). To properly assess the physiological role of a particular reaction or set of reactions characterized in vitro, it is important to consider the possible influence of crowding and/or confinement upon the reaction in its physiological milieu.

Subfields: Biophysics, Cell Biology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/bdf3dff7b4eace45e8f189df964bdbb992488dd1

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Citations in the corpus

Universally Sloppy Parameter Sensitivities in Systems Biology Models (2007, methodology): “[9] Minton AP (2001) The influence of macromolecular”
Α-synuclein misfolding and Parkinson's disease. (2012, background): “Obviously, the volume occupied by solutes is unavailable to other molecules, a phenomenon known as “excluded volume effects” [195, 199].”
Hydrophobicity: an ancient damage-associated molecular pattern that initiates innate immune responses (2004, background): “As a result of such high concentrations, hydrophobic molecules should aggregate even more rapidly in the cytoplasm than we would expect in dilute solution”
Towards an Understanding of the Temperature/ Pressure Configurational and Free-Energy Landscape of Biomolecules (2007, positive): “In addition, the presence of other biomolecules in the cell a¤ects the folding, stability, and function of proteins (socalled molecular crowding e¤ect [80]).”
3D domain swapping: As domains continue to swap (2002, background): “The effect of other macromolecules on a specific macromolecule in cells has been studied and termed “macromolecular crowding” (Minton 2001).”
Anomalous diffusion of proteins due to molecular crowding. (2005, background): “It is also known to cause depletion interactions, which tend to segregate macromolecules according to their size due to the increase in free volume accessible to the solutes upon segregation (14) and to affect the rates of chemical reactions taking place in solution (13,15).”
Molecular Simulations of Cotranslational Protein Folding: Fragment Stabilities, Folding Cooperativity, and Trapping in the Ribosome (2006, positive): “]. Finally, both the kinetics and thermodynamics of protein folding, and the potential for aggregation, may be significantly affected by the highly crowded conditions encountered physiologically [”
How a protein searches for its site on DNA: the mechanism of facilitated diffusion (2009, background): “Given that the macromolecules occupy 10%–40% of the total cellular volume (which corresponds to a concentration of ∼100–300 mgml [31, 38]), they are expected to have a non-negligible effect on search kinetics.”