A systematic investigation of the rate laws valid in intracellular environments


Recently there has been significant interest in deducing the form of the rate laws for chemical reactions occurring in the intracellular environment. This environment is typically characterized by low-dimensionality and a high macromolecular content; this leads to a spatial heterogeneity not typical of the well stirred in vitro environments. For this reason, the classical law of mass action has been presumed to be invalid for modeling intracellular reactions. Using lattice-gas automata models, it has recently been postulated [H. Berry, Monte Carlo simulations of enzyme reactions in two dimensions: Fractal kinetics and spatial segregation, Biophys. J. 83 (2002) 1891-1901; S. Schnell, T.E. Turner, Reaction kinetics in intracellular environments with macromolecular crowding: simulations and rate laws, Prog. Biophys. Mol. Biol. 85 (2004) 235-260] that the reaction kinetics is fractal-like. In this article we systematically investigate for the first time how the rate laws describing intracellular reactions vary as a function of: the geometry and size of the intracellular surface on which the reactions occur, the mobility of the macromolecules responsible for the crowding effects, the initial reactant concentrations and the probability of reaction between two reactant molecules. We also compare the rate laws valid in heterogeneous environments in which there is an underlying spatial lattice, for example crystalline alloys, with the rate laws valid in heterogeneous environments where there is no such natural lattice, for example in intracellular environments. Our simulations indicate that: (i) in intracellular environments both fractal kinetics and mass action can be valid, the major determinant being the probability of reaction. (ii) the geometry and size of the intracellular surface on which reactions are occurring does not significantly affect the rate law, (iii) there are considerable differences between the rate laws valid in heterogeneous non-living structures such as crystals and those valid in intracellular environments. Deviations from mass action are less pronounced in intracellular environments than in a crystalline material of similar heterogeneity. (c) 2006 Elsevier B.V. All rights reserved.