29,391 research outputs found
The Nondeterministic Waiting Time Algorithm: A Review
We present briefly the Nondeterministic Waiting Time algorithm. Our technique
for the simulation of biochemical reaction networks has the ability to mimic
the Gillespie Algorithm for some networks and solutions to ordinary
differential equations for other networks, depending on the rules of the
system, the kinetic rates and numbers of molecules. We provide a full
description of the algorithm as well as specifics on its implementation. Some
results for two well-known models are reported. We have used the algorithm to
explore Fas-mediated apoptosis models in cancerous and HIV-1 infected T cells
Energy-based Analysis of Biochemical Cycles using Bond Graphs
Thermodynamic aspects of chemical reactions have a long history in the
Physical Chemistry literature. In particular, biochemical cycles - the
building-blocks of biochemical systems - require a source of energy to
function. However, although fundamental, the role of chemical potential and
Gibb's free energy in the analysis of biochemical systems is often overlooked
leading to models which are physically impossible. The bond graph approach was
developed for modelling engineering systems where energy generation, storage
and transmission are fundamental. The method focuses on how power flows between
components and how energy is stored, transmitted or dissipated within
components. Based on early ideas of network thermodynamics, we have applied
this approach to biochemical systems to generate models which automatically
obey the laws of thermodynamics. We illustrate the method with examples of
biochemical cycles. We have found that thermodynamically compliant models of
simple biochemical cycles can easily be developed using this approach. In
particular, both stoichiometric information and simulation models can be
developed directly from the bond graph. Furthermore, model reduction and
approximation while retaining structural and thermodynamic properties is
facilitated. Because the bond graph approach is also modular and scaleable, we
believe that it provides a secure foundation for building thermodynamically
compliant models of large biochemical networks
Roadmap on semiconductor-cell biointerfaces.
This roadmap outlines the role semiconductor-based materials play in understanding the complex biophysical dynamics at multiple length scales, as well as the design and implementation of next-generation electronic, optoelectronic, and mechanical devices for biointerfaces. The roadmap emphasizes the advantages of semiconductor building blocks in interfacing, monitoring, and manipulating the activity of biological components, and discusses the possibility of using active semiconductor-cell interfaces for discovering new signaling processes in the biological world
Chemical Power for Microscopic Robots in Capillaries
The power available to microscopic robots (nanorobots) that oxidize
bloodstream glucose while aggregated in circumferential rings on capillary
walls is evaluated with a numerical model using axial symmetry and
time-averaged release of oxygen from passing red blood cells. Robots about one
micron in size can produce up to several tens of picowatts, in steady-state, if
they fully use oxygen reaching their surface from the blood plasma. Robots with
pumps and tanks for onboard oxygen storage could collect oxygen to support
burst power demands two to three orders of magnitude larger. We evaluate
effects of oxygen depletion and local heating on surrounding tissue. These
results give the power constraints when robots rely entirely on ambient
available oxygen and identify aspects of the robot design significantly
affecting available power. More generally, our numerical model provides an
approach to evaluating robot design choices for nanomedicine treatments in and
near capillaries.Comment: 28 pages, 7 figure
Emergence of the mitochondrial reticulum from fission and fusion dynamics
Mitochondria form a dynamic tubular reticulum within eukaryotic cells. Currently, quantitative understanding of its morphological characteristics is largely absent, despite major progress in deciphering the molecular fission and fusion machineries shaping its structure. Here we address the principles of formation and the large-scale organization of the cell-wide network of mitochondria. On the basis of experimentally determined structural features we establish the tip-to-tip and tip-to-side fission and fusion events as dominant reactions in the motility of this organelle. Subsequently, we introduce a graph-based model of the chondriome able to encompass its inherent variability in a single framework. Using both mean-field deterministic and explicit stochastic mathematical methods we establish a relationship between the chondriome structural network characteristics and underlying kinetic rate parameters. The computational analysis indicates that mitochondrial networks exhibit a percolation threshold. Intrinsic morphological instability of the mitochondrial reticulum resulting from its vicinity to the percolation transition is proposed as a novel mechanism that can be utilized by cells for optimizing their functional competence via dynamic remodeling of the chondriome. The detailed size distribution of the network components predicted by the dynamic graph representation introduces a relationship between chondriome characteristics and cell function. It forms a basis for understanding the architecture of mitochondria as a cell-wide but inhomogeneous organelle. Analysis of the reticulum adaptive configuration offers a direct clarification for its impact on numerous physiological processes strongly dependent on mitochondrial dynamics and organization, such as efficiency of cellular metabolism, tissue differentiation and aging
Introducing spatial information into predictive NF-kappa B modelling - an agent-based approach
Nature is governed by local interactions among lower-level sub-units, whether at the cell, organ, organism, or colony level. Adaptive system behaviour emerges via these interactions, which integrate the activity of the sub-units. To understand the system level it is necessary to understand the underlying local interactions. Successful models of local interactions at different levels of biological organisation, including epithelial tissue and ant colonies, have demonstrated the benefits of such 'agent-based' modelling [1-4]. Here we present an agent-based approach to modelling a crucial biological system the intracellular NF-kappa B signalling pathway. The pathway is vital to immune response regulation, and is fundamental to basic survival in a range of species [5-7]. Alterations in pathway regulation underlie a variety of diseases, including atherosclerosis and arthritis. Our modelling of individual molecules, receptors and genes provides a more comprehensive outline of regulatory network mechanisms than previously possible with equation-based approaches [8]. The method also permits consideration of structural parameters in pathway regulation; here we predict that inhibition of NF-kappa B is directly affected by actin filaments of the cytoskeleton sequestering excess inhibitors, therefore regulating steady-state and feedback behaviour
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