title: A reaction-diffusion model of cytosolic hydrogen peroxide.
abstract: As a signaling molecule in mammalian cells, hydrogen peroxide (H2O2) determines the thiol/disulfide oxidation state of several key proteins in the cytosol. Localization is a key concept in redox signaling; the concentrations of signaling molecules within the cell are expected to vary in time and in space in manner that is essential for function. However, as a simplification, all theoretical studies of intracellular hydrogen peroxide and many experimental studies to date have treated the cytosol as a well-mixed compartment. In this work, we incorporate our previously reported reduced kinetic model of the network of reactions that metabolize hydrogen peroxide in the cytosol into a model that explicitly treats diffusion along with reaction. We modeled a bolus addition experiment, solved the model analytically, and used the resulting equations to quantify the spatiotemporal variations in intracellular H2O2 that result from this kind of perturbation to the extracellular H2O2 concentration. We predict that micromolar bolus additions of H2O2 to suspensions of HeLa cells (0.8 × 10(9)cells/l) result in increases in the intracellular concentration that are localized near the membrane. These findings challenge the assumption that intracellular concentrations of H2O2 are increased uniformly throughout the cell during bolus addition experiments and provide a theoretical basis for differing phenotypic responses of cells to intracellular versus extracellular perturbations to H2O2 levels.
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Lim
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Troy F
authors.initials: TF
authors.lastname: Langford
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Beijing K
authors.initials: BK
authors.lastname: Huang
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: William M
authors.initials: WM
authors.lastname: Deen
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. Electronic address: sikes@mit.edu.
authors.forename: Hadley D
authors.initials: HD
authors.lastname: Sikes
mesh_terms: D003600:Cytosol / Q000378:metabolism*; D004058:Diffusion; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000378:metabolism*
chemical_list: D006861:Hydrogen Peroxide
keywords: Cytosol; Hydrogen peroxide; Membrane gradient; Pseudo-steady state; Reaction-diffusion model; Redox signaling