53,052 research outputs found
Method for finding metabolic properties based on the general growth law. Liver examples. A General framework for biological modeling
We propose a method for finding metabolic parameters of cells, organs and
whole organisms, which is based on the earlier discovered general growth law.
Based on the obtained results and analysis of available biological models, we
propose a general framework for modeling biological phenomena and discuss how
it can be used in Virtual Liver Network project. The foundational idea of the
study is that growth of cells, organs, systems and whole organisms, besides
biomolecular machinery, is influenced by biophysical mechanisms acting at
different scale levels. In particular, the general growth law uniquely defines
distribution of nutritional resources between maintenance needs and biomass
synthesis at each phase of growth and at each scale level. We exemplify the
approach considering metabolic properties of growing human and dog livers and
liver transplants. A procedure for verification of obtained results has been
introduced too. We found that two examined dogs have high metabolic rates
consuming about 0.62 and 1 gram of nutrients per cubic centimeter of liver per
day, and verified this using the proposed verification procedure. We also
evaluated consumption rate of nutrients in human livers, determining it to be
about 0.088 gram of nutrients per cubic centimeter of liver per day for males,
and about 0.098 for females. This noticeable difference can be explained by
evolutionary development, which required females to have greater liver
processing capacity to support pregnancy. We also found how much nutrients go
to biomass synthesis and maintenance at each phase of liver and liver
transplant growth. Obtained results demonstrate that the proposed approach can
be used for finding metabolic characteristics of cells, organs, and whole
organisms, which can further serve as important inputs for many applications in
biology (protein expression), biotechnology (synthesis of substances), and
medicine.Comment: 20 pages, 6 figures, 4 table
Data-driven modelling of biological multi-scale processes
Biological processes involve a variety of spatial and temporal scales. A
holistic understanding of many biological processes therefore requires
multi-scale models which capture the relevant properties on all these scales.
In this manuscript we review mathematical modelling approaches used to describe
the individual spatial scales and how they are integrated into holistic models.
We discuss the relation between spatial and temporal scales and the implication
of that on multi-scale modelling. Based upon this overview over
state-of-the-art modelling approaches, we formulate key challenges in
mathematical and computational modelling of biological multi-scale and
multi-physics processes. In particular, we considered the availability of
analysis tools for multi-scale models and model-based multi-scale data
integration. We provide a compact review of methods for model-based data
integration and model-based hypothesis testing. Furthermore, novel approaches
and recent trends are discussed, including computation time reduction using
reduced order and surrogate models, which contribute to the solution of
inference problems. We conclude the manuscript by providing a few ideas for the
development of tailored multi-scale inference methods.Comment: This manuscript will appear in the Journal of Coupled Systems and
Multiscale Dynamics (American Scientific Publishers
Computational and Mathematical Modelling of the EGF Receptor System
This chapter gives an overview of computational and mathematical modelling of the EGF receptor system. It begins with a survey of motivations for producing such models, then describes the main approaches that are taken to carrying out such modelling, viz. differential equations and individual-based modelling. Finally, a number of projects that applying modelling and simulation techniques to various aspects of the EGF receptor system are described
Reaction Brownian Dynamics and the effect of spatial fluctuations on the gain of a push-pull network
Brownian Dynamics algorithms are widely used for simulating soft-matter and
biochemical systems. In recent times, their application has been extended to
the simulation of coarse-grained models of cellular networks in simple
organisms. In these models, components move by diffusion, and can react with
one another upon contact. However, when reactions are incorporated into a
Brownian Dynamics algorithm, attention must be paid to avoid violations of the
detailed-balance rule, and therefore introducing systematic errors in the
simulation. We present a Brownian Dynamics algorithm for reaction-diffusion
systems that rigorously obeys detailed balance for equilibrium reactions. By
comparing the simulation results to exact analytical results for a bimolecular
reaction, we show that the algorithm correctly reproduces both equilibrium and
dynamical quantities. We apply our scheme to a ``push-pull'' network in which
two antagonistic enzymes covalently modify a substrate. Our results highlight
that the diffusive behaviour of the reacting species can reduce the gain of the
response curve of this network.Comment: 25 pages, 7 figures, submitted to Journal of Chemical Physic
Collective effects in intra-cellular molecular motor transport: coordination, cooperation and competetion
Molecular motors do not work in isolation {\it in-vivo}. We highlight some of
the coordinations, cooperations and competitions that determine the collective
properties of molecular motors in eukaryotic cells. In the context of
traffic-like movement of motors on a track, we emphasize the importance of
single-motor bio-chemical cycle and enzymatic activity on their collective
spatio-temporal organisation. Our modelling strategy is based on a synthesis-
the same model describes the single-motor mechano-chemistry at sufficiently low
densities whereas at higher densities it accounts for the collective flow
properties and the density profiles of the motors. We consider two specific
examples, namely, traffic of single-headed kinesin motors KIF1A on a
microtubule track and ribosome traffic on a messenger RNA track.Comment: 9 pages including LATEX text and 9 EPS figure
Control of Spatially Heterogeneous and Time-Varying Cellular Reaction Networks: A New Summation Law
A hallmark of a plethora of intracellular signaling pathways is the spatial
separation of activation and deactivation processes that potentially results in
precipitous gradients of activated proteins. The classical Metabolic Control
Analysis (MCA), which quantifies the influence of an individual process on a
system variable as the control coefficient, cannot be applied to spatially
separated protein networks. The present paper unravels the principles that
govern the control over the fluxes and intermediate concentrations in spatially
heterogeneous reaction networks. Our main results are two types of the control
summation theorems. The first type is a non-trivial generalization of the
classical theorems to systems with spatially and temporally varying
concentrations. In this generalization, the process of diffusion, which enters
as the result of spatial concentration gradients, plays a role similar to other
processes such as chemical reactions and membrane transport. The second
summation theorem is completely novel. It states that the control by the
membrane transport, the diffusion control coefficient multiplied by two, and a
newly introduced control coefficient associated with changes in the spatial
size of a system (e.g., cell), all add up to one and zero for the control over
flux and concentration. Using a simple example of a kinase/phosphatase system
in a spherical cell, we speculate that unless active mechanisms of
intracellular transport are involved, the threshold cell size is limited by the
diffusion control, when it is beginning to exceed the spatial control
coefficient significantly.Comment: 19 pages, AMS-LaTeX, 6 eps figures included with geompsfi.st
The macroscopic effects of microscopic heterogeneity
Over the past decade, advances in super-resolution microscopy and
particle-based modeling have driven an intense interest in investigating
spatial heterogeneity at the level of single molecules in cells. Remarkably, it
is becoming clear that spatiotemporal correlations between just a few molecules
can have profound effects on the signaling behavior of the entire cell. While
such correlations are often explicitly imposed by molecular structures such as
rafts, clusters, or scaffolds, they also arise intrinsically, due strictly to
the small numbers of molecules involved, the finite speed of diffusion, and the
effects of macromolecular crowding. In this chapter we review examples of both
explicitly imposed and intrinsic correlations, focusing on the mechanisms by
which microscopic heterogeneity is amplified to macroscopic effect.Comment: 20 pages, 5 figures. To appear in Advances in Chemical Physic
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