Monte carlo simulations of enzyme reactions in two dimensions: fractal kinetics and spatial segregation.

Conventional equations for enzyme kinetics are based on mass-action laws, that may fail in low-dimensional and disordered media such as biological membranes. We present Monte Carlo simulations of an isolated Michaelis-Menten enzyme reaction on two-dimensional lattices with varying obstacle densities, as models of biological membranes. The model predicts that, as a result of anomalous diffusion on these low-dimensional media, the kinetics are of the fractal type. Consequently, the conventional equations for enzyme kinetics fail to describe the reaction. In particular, we show that the quasi-stationary-state assumption can hardly be retained in these conditions. Moreover, the fractal characteristics of the kinetics are increasingly pronounced as obstacle density and initial substrate concentration increase. The simulations indicate that these two influences are mainly additive. Finally, the simulations show pronounced S-P segregation over the lattice at obstacle densities compatible with in vivo conditions. This phenomenon could be a source of spatial self organization in biological membranes.

[1]  M. Saxton,et al.  Lateral diffusion in an archipelago. Distance dependence of the diffusion coefficient. , 1989, Biophysical journal.

[2]  J. Bouchaud,et al.  Anomalous diffusion in disordered media: Statistical mechanisms, models and physical applications , 1990 .

[3]  M. Saxton,et al.  Lateral diffusion in an archipelago. Effects of impermeable patches on diffusion in a cell membrane. , 1982, Biophysical journal.

[4]  D. Torney,et al.  Diffusion-limited reaction rate theory for two-dimensional systems , 1983, Proceedings of the Royal Society of London. A. Mathematical and Physical Sciences.

[5]  S. Solomon,et al.  The importance of being discrete: life always wins on the surface. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[6]  Adam Lipowski,et al.  Nonequilibrium phase transition in a lattice prey–predator system , 2000 .

[7]  F. Wilczek,et al.  Particle–antiparticle annihilation in diffusive motion , 1983 .

[8]  M. Sahini,et al.  Applications of Percolation Theory , 2023, Applied Mathematical Sciences.

[9]  Sidney Redner,et al.  Scaling approach for the kinetics of recombination processes , 1984 .

[10]  Redner,et al.  Fluctuation-dominated kinetics in diffusion-controlled reactions. , 1985, Physical review. A, General physics.

[11]  J Langowski,et al.  Anomalous diffusion of fluorescent probes inside living cell nuclei investigated by spatially-resolved fluorescence correlation spectroscopy. , 2000, Journal of molecular biology.

[12]  West,et al.  Steady-state segregation in diffusion-limited reactions. , 1988, Physical review letters.

[13]  P. Argyrakis,et al.  Diffusion-limited binary reactions: the hierarchy of nonclassical regimes for random initial conditions , 1993 .

[14]  Shlesinger,et al.  Breakdown of Ovchinnikov-Zeldovich Segregation in the A+B-->0 Reaction under Lévy Mixing. , 1996, Physical review letters.

[15]  Kopelman,et al.  Nearest-neighbor distance distributions and self-ordering in diffusion-controlled reactions. II. A+B simulations. , 1990, Physical review. A, Atomic, molecular, and optical physics.

[16]  P. Argyrakis,et al.  Fractal to Euclidean crossover and scaling for random walkers on percolation clusters , 1984 .

[17]  N. Rashevsky,et al.  Mathematical biology , 1961, Connecticut medicine.

[18]  Pierre L'Ecuyer,et al.  Implementing a random number package with splitting facilities , 1991, TOMS.

[19]  Shlomo Havlin,et al.  Exact-enumeration approach to random walks on percolation clusters in two dimensions , 1984 .

[20]  A. Minton,et al.  Molecular crowding: analysis of effects of high concentrations of inert cosolutes on biochemical equilibria and rates in terms of volume exclusion. , 1998, Methods in enzymology.

[21]  J. R. Abney,et al.  Dynamics, structure, and function are coupled in the mitochondrial matrix. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[22]  Simulation of enzymatic cellular reactions complicated by phase separation. , 2000, Physical review. E, Statistical, nonlinear, and soft matter physics.

[23]  A. Verkman Solute and macromolecule diffusion in cellular aqueous compartments. , 2002, Trends in biochemical sciences.

[24]  W. R. Young,et al.  Reproductive pair correlations and the clustering of organisms , 2001, Nature.

[25]  P. G. de Gennes,et al.  Kinetics of diffusion‐controlled processes in dense polymer systems. I. Nonentangled regimes , 1982 .

[26]  E. Montroll,et al.  Random Walks on Lattices. II , 1965 .

[27]  S. Havlin,et al.  Diffusion in disordered media , 1991 .

[28]  A. Minton,et al.  Macromolecular crowding and molecular recognition , 1993, Journal of molecular recognition : JMR.

[29]  S. Sachdev Quantum Phase Transitions , 1999 .

[30]  D. Taylor,et al.  Hindered diffusion of inert tracer particles in the cytoplasm of mouse 3T3 cells. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[31]  M. Saxton,et al.  Lateral diffusion in an archipelago. Single-particle diffusion. , 1993, Biophysical journal.

[32]  Raoul Kopelman,et al.  Rate processes on fractals: Theory, simulations, and experiments , 1986 .

[33]  Kopelman,et al.  Diffusion-controlled binary reactions in low dimensions: Refined simulations. , 1992, Physical review. A, Atomic, molecular, and optical physics.

[34]  Raoul Kopelman,et al.  Fractal Reaction Kinetics , 1988, Science.

[35]  A. M. Turing,et al.  The chemical basis of morphogenesis , 1952, Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences.

[36]  Michael J. Saxton,et al.  Chapter 8 Lateral Diffusion of Lipids and Proteins , 1999 .

[37]  A. A. Ovchinnikov,et al.  Role of density fluctuations in bimolecular reaction kinetics , 1978 .

[38]  J. Linderman,et al.  Calculation of diffusion-limited kinetics for the reactions in collision coupling and receptor cross-linking. , 1997, Biophysical journal.

[39]  E. Montroll Random walks on lattices , 1969 .

[40]  “Quantum phase transitions” in classical nonequilibrium processes , 1999, cond-mat/9908450.

[41]  Steady-state chemical kinetics on surface clusters and islands: segregation of reactants , 1988 .

[42]  Spatially Resolved Anomalous Kinetics of a Catalytic Reaction: Enzymatic Glucose Oxidation in Capillary Spaces , 1997 .

[43]  M. Savageau Michaelis-Menten mechanism reconsidered: implications of fractal kinetics. , 1995, Journal of theoretical biology.

[44]  M. Delbruck,et al.  Structural Chemistry and Molecular Biology , 1968 .

[45]  M. Smoluchowski Versuch einer mathematischen Theorie der Koagulationskinetik kolloider Lösungen , 1918 .

[46]  M. Saxton Anomalous diffusion due to obstacles: a Monte Carlo study. , 1994, Biophysical journal.

[47]  Frank Moss,et al.  What is biological physics , 1997 .

[48]  J. Korlach,et al.  Fluorescence correlation spectroscopy with single-molecule sensitivity on cell and model membranes. , 1999, Cytometry.

[49]  Kopelman,et al.  Steady-state chemical kinetics on fractals: Segregation of reactants. , 1987, Physical review letters.

[50]  Lydéric Bocquet,et al.  Reduction of dimensionality in a diffusion search process and kinetics of gene expression , 2000 .

[51]  Kopelman,et al.  Nonclassical kinetics in three dimensions: Simulations of elementary A+B and A+A reactions. , 1996, Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics.