Controlling the rates of biochemical reactions and signaling networks by shape and volume changes

In biological systems, chemical activity takes place in micrometer- and nanometer-sized compartments that constantly change in shape and volume. These ever-changing cellular compartments embed chemical reactions, and we demonstrate that the rates of such incorporated reactions are directly affected by the ongoing shape reconfigurations. First, we show that the rate of product formation in an enzymatic reaction can be regulated by simple volume contraction–dilation transitions. The results suggest that mitochondria may regulate the dynamics of interior reaction pathways (e.g., the Krebs cycle) by volume changes. We then show the effect of shape changes on reactions occurring in more complex and structured systems by using biomimetic networks composed of micrometer-sized compartments joined together by nanotubes. Chemical activity was measured by implementing an enzymatic reaction–diffusion system. During ongoing reactions, the network connectivity is changed suddenly (similar to the dynamic tube formations found inside Golgi stacks, for example), and the effect on the reaction is registered. We show that spatiotemporal properties of the reaction–diffusion system are extremely sensitive to sudden changes in network topology and that chemical reactions can be initiated, or boosted, in certain nodes as a function of connectivity.

[1]  Zoran Konkoli Interplay between chemical reactions and transport in structured spaces. , 2005, Physical review. E, Statistical, nonlinear, and soft matter physics.

[2]  D. Häussinger,et al.  Functional significance of cell volume regulatory mechanisms. , 1998, Physiological reviews.

[3]  J. Knowles,et al.  Cloning, overexpression and mechanistic studies of carboxyphosphonoenolpyruvate mutase from Streptomyces hygroscopicus. , 1992, European journal of biochemistry.

[4]  B. Stoll,et al.  Control of liver cell function by the hydration state. , 1994, Biochemical Society Transactions.

[5]  Jennifer Lippincott-Schwartz,et al.  ER-to-Golgi transport visualized in living cells , 1997, Nature.

[6]  V. Choubey,et al.  Mitochondrial Swelling Impairs the Transport of Organelles in Cerebellar Granule Neurons* , 2007, Journal of Biological Chemistry.

[7]  E. Klipp,et al.  Integrative model of the response of yeast to osmotic shock , 2005, Nature Biotechnology.

[8]  R. Colman,et al.  Thr373, Asp375, and Lys260 are in the coenzyme site of porcine NADP-dependent isocitrate dehydrogenase. , 2006, Archives of biochemistry and biophysics.

[9]  William H. Press,et al.  Numerical recipes in C. The art of scientific computing , 1987 .

[10]  D. Häussinger,et al.  Alkalinization of acidic cellular compartments following cell swelling , 1994, FEBS letters.

[11]  L. Lizana,et al.  Diffusive transport in networks built of containers and tubes. , 2005, Physical review. E, Statistical, nonlinear, and soft matter physics.

[12]  A. Hall,et al.  Rho GTPases and the control of cell behaviour. , 2005, Biochemical Society transactions.

[13]  Zoran Konkoli,et al.  Diffusion-controlled reactions in small and structured spaces as a tool for describing living cell biochemistry , 2007 .

[14]  N J Russell,et al.  Citrate synthase and 2-methylcitrate synthase: structural, functional and evolutionary relationships. , 1998, Microbiology.

[15]  L. Packer SIZE AND SHAPE TRANSFORMATIONS CORRELATED WITH OXIDATIVE PHOSPHORYLATION IN MITOCHONDRIA. I. SWELLING-SHRINKAGE MECHANISMS IN INTACT MITOCHONDRIA. , 1963 .

[16]  U. Becherer,et al.  Vesicle pools, docking, priming, and release , 2006, Cell and Tissue Research.

[17]  H. Gerdes,et al.  Tunneling nanotubes: A new route for the exchange of components between animal cells , 2007, FEBS letters.

[18]  D. Chan Mitochondria: Dynamic Organelles in Disease, Aging, and Development , 2006, Cell.

[19]  C. Bakal,et al.  Quantitative Morphological Signatures Define Local Signaling Networks Regulating Cell Morphology , 2007, Science.

[20]  M. Elowitz,et al.  A synthetic oscillatory network of transcriptional regulators , 2000, Nature.

[21]  M. Neil,et al.  Structurally Distinct Membrane Nanotubes between Human Macrophages Support Long-Distance Vesicular Traffic or Surfing of Bacteria1 , 2006, The Journal of Immunology.

[22]  Kristin Sott,et al.  Micropipet-Assisted Formation of Microscopic Networks of Unilamellar Lipid Bilayer Nanotubes and Containers , 2001 .

[23]  J. Keizer Biochemical Oscillations and Cellular Rhythms: The molecular bases of periodic and chaotic behaviour, by Albert Goldbeter , 1998 .

[24]  D. Odde,et al.  Potential for Control of Signaling Pathways via Cell Size and Shape , 2006, Current Biology.

[25]  D. Häussinger,et al.  Regulation of cell function by the cellular hydration state. , 1994, The American journal of physiology.

[26]  D. Chiu,et al.  Formation of geometrically complex lipid nanotube-vesicle networks of higher-order topologies , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[27]  O. Orwar,et al.  Controlling enzymatic reactions by geometry in a biomimetic nanoscale network. , 2006, Nano letters.

[28]  M. McNiven,et al.  Vesicle Formation at the Plasma Membrane and Trans-Golgi Network: The Same but Different , 2006, Science.

[29]  V. Bunik,et al.  Kinetic properties of the 2-oxoglutarate dehydrogenase complex from Azotobacter vinelandii evidence for the formation of a precatalytic complex with 2-oxoglutarate. , 2000, European journal of biochemistry.

[30]  J. Shaw,et al.  Mitochondrial morphology and dynamics in yeast and multicellular eukaryotes. , 2005, Annual review of genetics.

[31]  Noah Sciaky,et al.  Golgi Tubule Traffic and the Effects of Brefeldin A Visualized in Living Cells , 1997, The Journal of cell biology.

[32]  W. Press,et al.  Numerical Recipes in Fortran: The Art of Scientific Computing.@@@Numerical Recipes in C: The Art of Scientific Computing. , 1994 .

[33]  A. Kaasik,et al.  Loss of mitochondrial membrane potential is associated with increase in mitochondrial volume: Physiological role in neurones , 2006, Journal of cellular physiology.

[34]  A. Luini,et al.  Secretory traffic triggers the formation of tubular continuities across Golgi sub-compartments , 2004, Nature Cell Biology.

[35]  K. Hahn,et al.  Activation of Endogenous Cdc42 Visualized in Living Cells , 2004, Science.