141 research outputs found
On Growth, Disorder, and Field Theory
This article reviews recent developments in statistical field theory far from
equilibrium. It focuses on the Kardar-Parisi-Zhang equation of stochastic
surface growth and its mathematical relatives, namely the stochastic Burgers
equation in fluid mechanics and directed polymers in a medium with quenched
disorder. At strong stochastic driving -- or at strong disorder, respectively
-- these systems develop nonperturbative scale-invariance. Presumably exact
values of the scaling exponents follow from a self-consistent asymptotic
theory. This theory is based on the concept of an operator product expansion
formed by the local scaling fields. The key difference to standard Lagrangian
field theory is the appearance of a dangerous irrelevant coupling constant
generating dynamical anomalies in the continuum limit.Comment: review article, 50 pages (latex), 10 figures (eps), minor
modification of original versio
Microscopic structure of travelling wave solutions in a class of stochastic interacting particle systems
We obtain exact travelling wave solutions for three families of stochastic
one-dimensional nonequilibrium lattice models with open boundaries. These
solutions describe the diffusive motion and microscopic structure of (i) of
shocks in the partially asymmetric exclusion process with open boundaries, (ii)
of a lattice Fisher wave in a reaction-diffusion system, and (iii) of a domain
wall in non-equilibrium Glauber-Kawasaki dynamics with magnetization current.
For each of these systems we define a microscopic shock position and calculate
the exact hopping rates of the travelling wave in terms of the transition rates
of the microscopic model. In the steady state a reversal of the bias of the
travelling wave marks a first-order non-equilibrium phase transition, analogous
to the Zel'dovich theory of kinetics of first-order transitions. The stationary
distributions of the exclusion process with shocks can be described in
terms of -dimensional representations of matrix product states.Comment: 27 page
Systems biologists seek fuller integration of systems biology approaches in new cancer research programs
Systems biology takes an interdisciplinary approach to the systematic study of complex interactions in biological systems. This approach seeks to decipher the emergent behaviors of complex systems rather than focusing only on their constituent properties. As an increasing number of examples illustrate the value of systems biology approaches to understand the initiation, progression, and treatment of cancer, systems biologists from across Europe and the United States hope for changes in the way their field is currently perceived among cancer researchers. In a recent EU-US workshop, supported by the European Commission, the German Federal Ministry for Education and Research, and the National Cancer Institute of the NIH, the participants discussed the strengths, weaknesses, hurdles, and opportunities in cancer systems biology
Alignment of cellular motility forces with tissue flow as a mechanism for efficient wound healing
Recent experiments have shown that spreading epithelial sheets
exhibit a long-range coordination of motility forces that leads to
a buildup of tension in the tissue, which may enhance cell division
and the speed of wound healing. Furthermore, the edges of these
epithelial sheets commonly show finger-like protrusions whereas the
bulk often displays spontaneous swirls of motile cells. To explain
these experimental observations, we propose a simple flocking-type
mechanism, in which cells tend to align their motility forceswith their
velocity. Implementing this idea in amechanical tissue simulation, the
proposed model gives rise to efficient spreading and can explain the
experimentally observed long-range alignment of motility forces in
highly disordered patterns, as well as the buildup of tensile stress
throughout the tissue. Our model also qualitatively reproduces the
dependence of swirl size and swirl velocity on cell density reported in
experiments and exhibits an undulation instability at the edge of the
spreading tissue commonly observed in vivo. Finally, we study the
dependence of colony spreading speed on important physical and
biological parameters and derive simple scaling relations that show
that coordination of motility forces leads to an improvement of the
wound healing process for realistic tissue parameters
Growth Based Morphogenesis of Vertebrate Limb Bud
Many genes and their regulatory relationships are involved in developmental phenomena. However, by chemical information alone, we cannot fully understand changing organ morphologies through tissue growth because deformation and growth of the organ are essentially mechanical processes. Here, we develop a mathematical model to describe the change of organ morphologies through cell proliferation. Our basic idea is that the proper specification of localized volume source (e.g., cell proliferation) is able to guide organ morphogenesis, and that the specification is given by chemical gradients. We call this idea “growth-based morphogenesis.” We find that this morphogenetic mechanism works if the tissue is elastic for small deformation and plastic for large deformation. To illustrate our concept, we study the development of vertebrate limb buds, in which a limb bud protrudes from a flat lateral plate and extends distally in a self-organized manner. We show how the proportion of limb bud shape depends on different parameters and also show the conditions needed for normal morphogenesis, which can explain abnormal morphology of some mutants. We believe that the ideas shown in the present paper are useful for the morphogenesis of other organs
Exploring hypotheses of the actions of TGF-beta 1 in epidermal wound healing using a 3D computational multiscale model of the human epidermis
In vivo and in vitro studies give a paradoxical picture of the actions of the key regulatory factor TGF-beta 1 in epidermal wound healing with it stimulating migration of keratinocytes but also inhibiting their proliferation. To try to reconcile these into an easily visualized 3D model of wound healing amenable for experimentation by cell biologists, a multiscale model of the formation of a 3D skin epithelium was established with TGF-beta 1 literature-derived rule sets and equations embedded within it. At the cellular level, an agent-based bottom-up model that focuses on individual interacting units ( keratinocytes) was used. This was based on literature-derived rules governing keratinocyte behavior and keratinocyte/ECM interactions. The selection of these rule sets is described in detail in this paper. The agent-based model was then linked with a subcellular model of TGF-beta 1 production and its action on keratinocytes simulated with a complex pathway simulator. This multiscale model can be run at a cellular level only or at a combined cellular/subcellular level. It was then initially challenged ( by wounding) to investigate the behavior of keratinocytes in wound healing at the cellular level. To investigate the possible actions of TGF-beta 1, several hypotheses were then explored by deliberately manipulating some of these rule sets at subcellular levels. This exercise readily eliminated some hypotheses and identified a sequence of spatial-temporal actions of TGF-beta 1 for normal successful wound healing in an easy-to-follow 3D model. We suggest this multiscale model offers a valuable, easy-to-visualize aid to our understanding of the actions of this key regulator in wound healing, and provides a model that can now be used to explore pathologies of wound healing
Agent based modelling helps in understanding the rules by which fibroblasts support keratinocyte colony formation
Background: Autologous keratincoytes are routinely expanded using irradiated mouse fibroblasts and bovine serum for clinical use. With growing concerns about the safety of these xenobiotic materials, it is desirable to culture keratinocytes in media without animal derived products. An improved understanding of epithelial/mesenchymal interactions could assist in this.
Methodology/Principal Findings: A keratincyte/fibroblast o-culture model was developed by extending an agent-based keratinocyte colony formation model to include the response of keratinocytes to both fibroblasts and serum. The model was validated by comparison of the in virtuo and in vitro multicellular behaviour of keratinocytes and fibroblasts in single and co-culture in Greens medium. To test the robustness of the model, several properties of the fibroblasts were changed to investigate their influence on the multicellular morphogenesis of keratinocyes and fibroblasts. The model was then used to generate hypotheses to explore the interactions of both proliferative and growth arrested fibroblasts with keratinocytes. The key predictions arising from the model which were confirmed by in vitro experiments were that 1) the ratio of fibroblasts to keratinocytes would critically influence keratinocyte colony expansion, 2) this ratio needed to be optimum at the beginning of the co-culture, 3) proliferative fibroblasts would be more effective than irradiated cells in expanding keratinocytes and 4) in the presence of an adequate number of fibroblasts, keratinocyte expansion would be independent of serum.
Conclusions: A closely associated computational and biological approach is a powerful tool for understanding complex biological systems such as the interactions between keratinocytes and fibroblasts. The key outcome of this study is the finding that the early addition of a critical ratio of proliferative fibroblasts can give rapid keratinocyte expansion without the use of irradiated mouse fibroblasts and bovine serum
Comparing individual-based approaches to modelling the self-organization of multicellular tissues.
The coordinated behaviour of populations of cells plays a central role in tissue growth and renewal. Cells react to their microenvironment by modulating processes such as movement, growth and proliferation, and signalling. Alongside experimental studies, computational models offer a useful means by which to investigate these processes. To this end a variety of cell-based modelling approaches have been developed, ranging from lattice-based cellular automata to lattice-free models that treat cells as point-like particles or extended shapes. However, it remains unclear how these approaches compare when applied to the same biological problem, and what differences in behaviour are due to different model assumptions and abstractions. Here, we exploit the availability of an implementation of five popular cell-based modelling approaches within a consistent computational framework, Chaste (http://www.cs.ox.ac.uk/chaste). This framework allows one to easily change constitutive assumptions within these models. In each case we provide full details of all technical aspects of our model implementations. We compare model implementations using four case studies, chosen to reflect the key cellular processes of proliferation, adhesion, and short- and long-range signalling. These case studies demonstrate the applicability of each model and provide a guide for model usage
Vascular network remodeling via vessel cooption, regression and growth in tumors
The transformation of the regular vasculature in normal tissue into a highly
inhomogeneous tumor specific capillary network is described by a theoretical
model incorporating tumor growth, vessel cooption, neo-vascularization, vessel
collapse and cell death. Compartmentalization of the tumor into several regions
differing in vessel density, diameter and in necrosis is observed for a wide
range of parameters in agreement with the vessel morphology found in human
melanoma. In accord with data for human melanoma the model predicts, that
microvascular density (MVD, regarded as an important diagnostic tool in cancer
treatment, does not necessarily determine the tempo of tumor progression.
Instead it is suggested, that the MVD of the original tissue as well as the
metabolic demand of the individual tumor cell plays the major role in the
initial stages of tumor growth.Comment: 30 pages, 11 figures (higher resolution at
http://www.uni-saarland.de/fak7/rieger/HOMEPAGE/BJ0.pdf
A Multicellular Model of Intestinal Crypt Buckling and Fission
Crypt fission is an in vivo tissue deformation process that is involved in both intestinal homeostasis and colorectal tumourigenesis. Despite its importance, the mechanics underlying crypt fission are currently poorly understood. Recent experimental development of organoids, organ-like buds cultured from crypt stem cells in vitro, has shown promise in shedding light on crypt fission. Drawing inspiration from observations of organoid growth and fission in vivo, we develop a computational model of a deformable epithelial tissue layer. Results from in silico experiments show the stiffness of cells and the proportions of cell subpopulations affect the nature of deformation in the epithelial layer. In particular, we find that increasing the proportion of stiffer cells in the layer increases the likelihood of crypt fission occurring. This is in agreement with and helps explain recent experimental work
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