scholarly journals Co-localization and confinement of ecto-nucleotidases modulate extracellular adenosine nucleotide pools

2019 ◽  
Author(s):  
Hadi Rahmaninejad ◽  
Tom Pace ◽  
Shashank Bhatt ◽  
Bin Sun ◽  
Peter M Kekenes-Huskey
Keyword(s):  
Electrostatic Interactions ◽  
Reaction Diffusion ◽  
Reaction Rates ◽  
Close Coupling ◽  
Reactive Protein ◽  
Diffusion Limited ◽  
Synaptic Junctions ◽  
Catalyzed Reactions ◽  
Coupled Enzymes ◽  
Net Charges

Nucleotides comprise small molecules that perform critical signaling and energetic roles in biological systems. Of these, the concentrations of adenosine and its derivatives, including adenosine tri-, di-, and mono-phosphate are dynamically controlled in the extracellular-space by ecto-nucleotidases that rapidly degrade such nucleotides. In many instances, the close coupling between cells such as those in synaptic junctions yields tiny extracellular 'nanodomains' within which the charged nucleotides interact with densely-packed membranes and biomolecules. While the contributions of electrostatic and steric interactions within such nanodomains are known to shape diffusion-limited reaction rates, less is understood about how these factors control the kinetics of sequentially-coupled ecto-nucleotidase-catalyzed reactions. To rank the relative importance of these factors, we utilize reaction-diffusion numerical simulations to systematically probe coupled enzyme activity in narrow junctions. We perform these simulations in nanoscale geometries representative of narrow extracellular compartments, within which we localize sequentially- and spatially-coupled enzymes. These enzymes catalyze the conversion of a representative charged substrate such as (ATP) into substrates with different net charges, such as (AMP) and (Ado). Our modeling approach considers electrostatic interactions of diffusing, charged substrates with extracellular membranes, and coupled enzymes. With this model, we find that 1) Reaction rates exhibited confinement effects, namely reduced reaction rates relative to bulk, that were most pronounced when the enzyme was close to the pore size and 2) The presence of charge on the pore boundary further tunes reaction rates by controlling the pooling of substrate near the reactive protein akin to ions near trans-membrane proteins. These findings suggest how remarkable reaction efficiencies of coupled enzymatic processes can be supported in charged and spatially-confined volumes of extracellular spaces.

DNA Binding To Conducting Polymer Films

1991 ◽  
Vol 255 ◽  
Author(s):  
Jeong-Ok Lim ◽  
Daniel S. Minehan ◽  
M. Kamath ◽  
Kenneth A. Marx ◽  
Sukant K. Tripathy
Keyword(s):  
Dna Binding ◽  
Electrochemical Reduction ◽  
Conducting Polymer ◽  
Polymer Films ◽  
Electrostatic Interactions ◽  
Positive Charge ◽  
Chemical Methods ◽  
Diffusion Limited ◽  
Conducting Polymer Films ◽  
Solution Uptake

AbstractThe polycation conducting polymers, oxidized polypyrrole and polyalkylthiophene, possess the ability to form complexes with polyanionic DNA molecules through largely electrostatic interactions. This study demonstrated the solution uptake and binding of 32p radiolabeled DNA by conducting polymer thick films (50–100μm). Polypyrrole (PPy) was synthesized by electrochemical methods and poly(3-hexylthiophene) (PHT) and poly(3-undecylthiophene) (PUT) were synthesized by chemical methods. The DNA binding rates on PPy films were affected by DNA concentration and the oxidation state (measured as conductivity). The DNA kinetics support a diffusion limited model for binding. We measured DNA binding levels onto all three polymer films; PUT, PHT, and PPy. The binding levels increased in the same order as the conductivities of the polymer films. DNA binding onto oxidized PPy film was diminished upon electrochemical reduction. These observations showed, therefore, the binding may be linked with the positive charge sites responsible for conduction in the polymer films.

A stochastic reaction-diffusion model for protein aggregation on DNA

2017 ◽  
Vol 28 (08) ◽  
pp. 1750102 ◽  
Author(s):  
Nikolaos K. Voulgarakis
Keyword(s):  
Electrostatic Interactions ◽  
Reaction Diffusion ◽  
Control Parameters ◽  
Physical Mechanisms ◽  
Softening Behavior ◽  
Vital Functions ◽  
Reaction Diffusion Model ◽  
Proposed Model ◽  
Negative Supercoiling ◽  
Stochastic Reaction

Vital functions of DNA, such as transcription and packaging, depend on the proper clustering of proteins on the double strand. The present study investigates how the interplay between DNA allostery and electrostatic interactions affects protein clustering. The statistical analysis of a simple but transparent computational model reveals two major consequences of this interplay. First, depending on the protein and salt concentration, protein filaments exhibit a bimodal DNA stiffening and softening behavior. Second, within a certain domain of the control parameters, electrostatic interactions can cause energetic frustration that forces proteins to assemble in rigid spiral configurations. Such spiral filaments might trigger both positive and negative supercoiling, which can ultimately promote gene compaction and regulate the promoter. It has been experimentally shown that bacterial histone-like proteins assemble in similar spiral patterns and/or exhibit the same bimodal behavior. The proposed model can, thus, provide computational insights into the physical mechanisms used by proteins to control the mechanical properties of the DNA.

scholarly journals Crowding within synaptic junctions influence the degradation of adenoside nucleotides by CD39 and CD73 ectonucleotidases

2021 ◽  
Author(s):  
Hadi Rahmaninejad ◽  
Tom Pace ◽  
Peter Kekenes-Huskey
Keyword(s):  
Electrostatic Interactions ◽  
Configurational Entropy ◽  
Reaction Diffusion ◽  
Adenosine Monophosphate ◽  
Adenosine Diphosphate ◽  
Surprising Result ◽  
Surface Charges ◽  
Association Rate ◽  
Synaptic Junction ◽  
Reaction Diffusion Model

Synapsed cells can communicate using exocytosed nucleotides like adenosine triphosphate (ATP). Ectonucleotidases localized to a synaptic junction degradesuch nucleotides into metabolites like adenosine monophosphate (AMP) or adenosine, oftentimes in a sequential manner. CD39 and CD73 are a representativeset of coupled ectonucleotidases, where CD39 first converts ATP and adenosine diphosphate (ADP) into AMP, after which the AMP product is dephosphorylated into adenosine by CD73. Hence, CD39/CD73 help shape cellular responses to extracellular ATP. In a previous study [1] we demonstrated that the rates of coupled CD39/CD73 activity within synapse-like junctions are strongly controlled by the enzymes' co-localization, their surface charge densities, and the electrostatic potential of the surrounding cell membranes. In this study, we demonstrate that crowders within a synaptic junction, which can include globular proteins like cytokines and membrane-bound proteins, impact coupled CD39/CD73 electronucleotidase activity and in turn, the availability of intrasynapse ATP. Specifically, we simulated a spatially-explicit, reaction-diffusion model for the coupled conversion of ATP -> AMP and AMP -> adenosine in a model synaptic junction with crowders via the finite element method. Our modeling results suggest that the association rate for ATP to CD39 is strongly influenced by the density of intrasynaptic protein crowders, as increasing crowder density suppressed ATP association kinetics. Much of this suppression can be rationalized based on a loss of configurational entropy. The surface charges of crowders can further influence the association rate, with the surprising result that favorable crowder/nucleotide electrostatic interactions can yield CD39 association rates that are faster than crowder-free configurations. However, attractive crowder/nucleotide interactions decrease the rate and efficiency of adenosine production, which in turn increases the availability of ATP and AMP within the synapse relative to crowder-free configurations. These findings highlight how CD39/CD73 ectonucleotidase activity, electrostatics and crowding within synapses influence the availability of nucleotides for intercellular communication.

Turing and Benjamin–Feir instability mechanisms in non-autonomous systems

2020 ◽  
Vol 476 (2238) ◽  
pp. 20200003 ◽  
Author(s):  
Robert A. Van Gorder
Keyword(s):  
Autonomous Systems ◽  
Reaction Diffusion ◽  
Reaction Rates ◽  
Time Dependent ◽  
Model Parameters ◽  
Time Varying ◽  
Reaction Diffusion Systems ◽  
Diffusion Systems ◽  
Dependent Model ◽  
Spatio Temporal

The Turing and Benjamin–Feir instabilities are two of the primary instability mechanisms useful for studying the transition from homogeneous states to heterogeneous spatial or spatio-temporal states in reaction–diffusion systems. We consider the case when the underlying reaction–diffusion system is non-autonomous or has a base state which varies in time, as in this case standard approaches, which rely on temporal eigenvalues, break down. We are able to establish respective criteria for the onset of each instability using comparison principles, obtaining inequalities which involve the in general time-dependent model parameters and their time derivatives. In the autonomous limit where the base state is constant in time, our results exactly recover the respective Turing and Benjamin–Feir conditions known in the literature. Our results make the Turing and Benjamin–Feir analysis amenable for a wide collection of applications, and allow one to better understand instabilities emergent due to a variety of non-autonomous mechanisms, including time-varying diffusion coefficients, time-varying reaction rates, time-dependent transitions between reaction kinetics and base states which change in time (such as heteroclinic connections between unique steady states, or limit cycles), to name a few examples.

Temperature, Dynamics, and Enzyme-Catalyzed Reaction Rates

2020 ◽  
Vol 49 (1) ◽  
pp. 163-180 ◽  
Author(s):  
Vickery L. Arcus ◽  
Adrian J. Mulholland
Keyword(s):  
Molecular Mechanisms ◽  
Activation Parameters ◽  
Reaction Rates ◽  
Rate Theory ◽  
Different Temperatures ◽  
State Ensemble ◽  
Catalyzed Reactions ◽  
Enzyme Catalyzed Reactions ◽  
Transition State Ensemble ◽  
Rate Limiting

We review the adaptations of enzyme activity to different temperatures. Psychrophilic (cold-adapted) enzymes show significantly different activation parameters (lower activation enthalpies and entropies) from their mesophilic counterparts. Furthermore, there is increasing evidence that the temperature dependence of many enzyme-catalyzed reactions is more complex than is widely believed. Many enzymes show curvature in plots of activity versus temperature that is not accounted for by denaturation or unfolding. This is explained by macromolecular rate theory: A negative activation heat capacity for the rate-limiting chemical step leads directly to predictions of temperature optima; both entropy and enthalpy are temperature dependent. Fluctuations in the transition state ensemble are reduced compared to the ground state. We show how investigations combining experiment with molecular simulation are revealing fundamental details of enzyme thermoadaptation that are relevant for understanding aspects of enzyme evolution. Simulations can calculate relevant thermodynamic properties (such as activation enthalpies, entropies, and heat capacities) and reveal the molecular mechanisms underlying experimentally observed behavior.

scholarly journals A Nonlocal Eigenvalue Problem and the Stability of Spikes for Reaction–Diffusion Systems with Fractional Reaction Rates

2003 ◽  
Vol 13 (06) ◽  
pp. 1529-1543 ◽  
Author(s):  
Juncheng Wei ◽  
Matthias Winter
Keyword(s):  
Eigenvalue Problem ◽  
Reaction Diffusion ◽  
Reaction Rates ◽  
Reaction Diffusion Systems ◽  
Diffusion Systems ◽  
The Stability ◽  
Nonlocal Eigenvalue Problem ◽  
Fractional Reaction

We consider a nonlocal eigenvalue problem which arises in the study of stability of spike solutions for reaction–diffusion systems with fractional reaction rates such as the Sel'kov model, the Gray–Scott system, the hypercycle of Eigen and Schuster, angiogenesis, and the generalized Gierer–Meinhardt system. We give some sufficient and explicit conditions for stability by studying the corresponding nonlocal eigenvalue problem in a new range of parameters.

Evaluation of Lattice Boltzmann Method for Reaction-Diffusion Process in a Porous SOFC Anode Microstructure

2012 ◽  
Author(s):  
Hedvig Paradis ◽  
Bengt Sundén
Keyword(s):  
Porous Media ◽  
Lattice Boltzmann Method ◽  
Lattice Boltzmann ◽  
Reaction Diffusion ◽  
Reaction Rates ◽  
Transport Processes ◽  
Microscopic Level ◽  
Reaction Diffusion Equation ◽  
Interaction Sites ◽  
Boltzmann Method

In the microscale structure of a porous electrode, the transport processes are among the least understood areas of SOFC. The purpose of this study is to evaluate the Lattice Boltzmann Method (LBM) for a porous microscopic media and investigate mass transfer processes with electrochemical reactions by LBM at a mesoscopic and microscopic level. Part of the anode structure of an SOFC for two components is evaluated qualitatively for two different geometry configurations of the porous media. The reaction-diffusion equation has been implemented in the particle distribution function used in LBM. The LBM code in this study is written in the programs MATLAB and Palabos. It has here been shown that LBM can be effectively used at a mesoscopic level ranging down to a microscopic level and proven to effectively take care of the interaction between the particles and the walls of the porous media. LBM can also handle the implementation of reaction rates where these can be locally specified or as a general source term. It is concluded that LBM can be valuable for evaluating the risk of local harming spots within the porous structure to reduce these interaction sites. In future studies, the information gained from the microscale modeling can be coupled to a macroscale CFD model and help in development of a smooth structure for interaction of the reforming reaction and the electrochemical reaction rates. This can in turn improve the cell performance.

scholarly journals Fullerene ion chemistry: a journey of discovery and achievement

2016 ◽  
Vol 374 (2076) ◽  
pp. 20150321 ◽  
Author(s):  
Diethard K. Böhme
Keyword(s):  
Electrostatic Interactions ◽  
Coulomb Repulsion ◽  
Reaction Rates ◽  
Chemistry Laboratory ◽  
Carbon Surface ◽  
Reaction Products ◽  
Ion Chemistry ◽  
Ion Formation ◽  
Multiply Charged ◽  
Buckminster Fullerene

An account is provided of the extraordinary features of buckminster fullerene cations and their chemistry that we discovered in our Ion Chemistry Laboratory at York University (Canada) during a ‘golden’ period of research in the early 1990s, just after C 60 powder became available. We identified new chemical ways of C 60 ionization and tracked novel chemistry of C 60 n + as a function of charge state ( n =1–3) with some 50 different reagent molecules. We found that multiple charges enhance reaction rates and diversify reaction products and mechanisms. Strong electrostatic interactions with reagent molecules were seen to reduce barriers to carbon surface bonding and charge-separation reactions, while intramolecular Coulomb repulsion appeared to localize charge on the surface or the substituent and so influence higher order chemistry, including ‘spindle’, ‘star’, ‘fuzzy ball’, ‘ball-and-chain’ and dimer ion formation. We introduced the notion of ‘apparent’ gas-phase acidity with measurements of proton-transfer reactions of multiply charged fullerene cations. We also explored the attachment of atomic metal cations to C 60 and their subsequent reactions. All these findings were applied to the possible chemistry of fullerene cations in the interstellar medium with a focus on multiply charged fullerene ion formation and the intervention of fullerene cations in fullerene derivatization and molecular synthesis, with a view to their possible future detection. This article is part of the themed issue ‘Fullerenes: past, present and future, celebrating the 30th anniversary of Buckminster Fullerene’.

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