25,973 research outputs found
A global sensitivity analysis approach for morphogenesis models
{\bf Background} %if any
Morphogenesis is a developmental process in which cells organize into shapes and patterns. Complex, non-linear and multi-factorial models with images as output are commonly used to study morphogenesis. It is difficult to understand the relation between the uncertainty in the input and the output of such `black-box' models, giving rise to the need for sensitivity analysis tools. In this paper, we introduce a workflow for a global sensitivity analysis approach to study the impact of single parameters and the interactions between them on the output of morphogenesis models.
{\bf Results} %if any
To demonstrate the workflow, we used a published, well-studied model of vascular morphogenesis. The parameters of this cellular Potts model (CPM) represent cell properties and behaviors that drive the mechanisms of angiogenic sprouting. The global sensitivity analysis correctly identified the dominant parameters in the model, consistent with previous studies. Additionally, the analysis provided information on the relative impact of single parameters and of interactions between them. This is very relevant because interactions of parameters impede the experimental verification of the predicted effect of single parameters. The parameter interactions, although of low impact, provided also new insights in the mechanisms of \emph{in silico} sprouting. Finally, the analysis indicated
that the model could be reduced by one parameter.
{\bf Conclusions} %if any
We propose global sensitivity analysis as an alternative approach to study the mechanisms of morphogenesis.
Comparison of the ranking of the impact of the model parameters to knowledge derived from experimental data and from manipulation experiments can help to falsify models and to find the operand mechanisms in morphogenesis. The workflow is applicable to all `black-box' models, including high-throughput \emph{in vitro} models in which output measures are affected by a set of experimental perturbations
Digital Tectonics as a Morphogenetic Process
p. 938-948Tectonics is a seminal concept that defines the nature of the relationship between
architecture and its structural properties. The changing definition of the symbiotic
relationship between structural engineering and architectural design may be considered one of the formative influences on the conceptual evolution of tectonics in different historical periods. Recent developments in the field of morphogenesis, digital media, theories techniques and methods of digital design have contributed a new models of integration between structure, material and form in digital tectonics.
The objective of this paper is to propose and define tectonics as a model of morphogenetic process. The paper identifies and presents the manner in which theory and emerging concepts of morphogenesis as well as digital models of design are contributing to this new model. The paper first analyzes the historical evolution of tectonics as a concept and characterizes the emergence of theoretical framework reflected in concepts and terms related to morphogenesis.Oxman, R. (2010). Digital Tectonics as a Morphogenetic Process. Editorial Universitat Politècnica de València. http://hdl.handle.net/10251/695
Cell-cell communication enhances the capacity of cell ensembles to sense shallow gradients during morphogenesis
Collective cell responses to exogenous cues depend on cell-cell interactions.
In principle, these can result in enhanced sensitivity to weak and noisy
stimuli. However, this has not yet been shown experimentally, and, little is
known about how multicellular signal processing modulates single cell
sensitivity to extracellular signaling inputs, including those guiding complex
changes in the tissue form and function. Here we explored if cell-cell
communication can enhance the ability of cell ensembles to sense and respond to
weak gradients of chemotactic cues. Using a combination of experiments with
mammary epithelial cells and mathematical modeling, we find that multicellular
sensing enables detection of and response to shallow Epidermal Growth Factor
(EGF) gradients that are undetectable by single cells. However, the advantage
of this type of gradient sensing is limited by the noisiness of the signaling
relay, necessary to integrate spatially distributed ligand concentration
information. We calculate the fundamental sensory limits imposed by this
communication noise and combine them with the experimental data to estimate the
effective size of multicellular sensory groups involved in gradient sensing.
Functional experiments strongly implicated intercellular communication through
gap junctions and calcium release from intracellular stores as mediators of
collective gradient sensing. The resulting integrative analysis provides a
framework for understanding the advantages and limitations of sensory
information processing by relays of chemically coupled cells.Comment: paper + supporting information, total 35 pages, 15 figure
Mechanical Stress Inference for Two Dimensional Cell Arrays
Many morphogenetic processes involve mechanical rearrangement of epithelial
tissues that is driven by precisely regulated cytoskeletal forces and cell
adhesion. The mechanical state of the cell and intercellular adhesion are not
only the targets of regulation, but are themselves likely signals that
coordinate developmental process. Yet, because it is difficult to directly
measure mechanical stress {\it in vivo} on sub-cellular scale, little is
understood about the role of mechanics of development. Here we present an
alternative approach which takes advantage of the recent progress in live
imaging of morphogenetic processes and uses computational analysis of high
resolution images of epithelial tissues to infer relative magnitude of forces
acting within and between cells. We model intracellular stress in terms of bulk
pressure and interfacial tension, allowing these parameters to vary from cell
to cell and from interface to interface. Assuming that epithelial cell layers
are close to mechanical equilibrium, we use the observed geometry of the two
dimensional cell array to infer interfacial tensions and intracellular
pressures. Here we present the mathematical formulation of the proposed
Mechanical Inverse method and apply it to the analysis of epithelial cell
layers observed at the onset of ventral furrow formation in the {\it
Drosophila} embryo and in the process of hair-cell determination in the avian
cochlea. The analysis reveals mechanical anisotropy in the former process and
mechanical heterogeneity, correlated with cell differentiation, in the latter
process. The method opens a way for quantitative and detailed experimental
tests of models of cell and tissue mechanics
Mathematical models for chemotaxis and their applications in self-organisation phenomena
Chemotaxis is a fundamental guidance mechanism of cells and organisms,
responsible for attracting microbes to food, embryonic cells into developing
tissues, immune cells to infection sites, animals towards potential mates, and
mathematicians into biology. The Patlak-Keller-Segel (PKS) system forms part of
the bedrock of mathematical biology, a go-to-choice for modellers and analysts
alike. For the former it is simple yet recapitulates numerous phenomena; the
latter are attracted to these rich dynamics. Here I review the adoption of PKS
systems when explaining self-organisation processes. I consider their
foundation, returning to the initial efforts of Patlak and Keller and Segel,
and briefly describe their patterning properties. Applications of PKS systems
are considered in their diverse areas, including microbiology, development,
immunology, cancer, ecology and crime. In each case a historical perspective is
provided on the evidence for chemotactic behaviour, followed by a review of
modelling efforts; a compendium of the models is included as an Appendix.
Finally, a half-serious/half-tongue-in-cheek model is developed to explain how
cliques form in academia. Assumptions in which scholars alter their research
line according to available problems leads to clustering of academics and the
formation of "hot" research topics.Comment: 35 pages, 8 figures, Submitted to Journal of Theoretical Biolog
Computational Screening of Tip and Stalk Cell Behavior Proposes a Role for Apelin Signaling in Sprout Progression
Angiogenesis involves the formation of new blood vessels by sprouting or
splitting of existing blood vessels. During sprouting, a highly motile type of
endothelial cell, called the tip cell, migrates from the blood vessels followed
by stalk cells, an endothelial cell type that forms the body of the sprout. To
get more insight into how tip cells contribute to angiogenesis, we extended an
existing computational model of vascular network formation based on the
cellular Potts model with tip and stalk differentiation, without making a
priori assumptions about the differences between tip cells and stalk cells. To
predict potential differences, we looked for parameter values that make tip
cells (a) move to the sprout tip, and (b) change the morphology of the
angiogenic networks. The screening predicted that if tip cells respond less
effectively to an endothelial chemoattractant than stalk cells, they move to
the tips of the sprouts, which impacts the morphology of the networks. A
comparison of this model prediction with genes expressed differentially in tip
and stalk cells revealed that the endothelial chemoattractant Apelin and its
receptor APJ may match the model prediction. To test the model prediction we
inhibited Apelin signaling in our model and in an \emph{in vitro} model of
angiogenic sprouting, and found that in both cases inhibition of Apelin or of
its receptor APJ reduces sprouting. Based on the prediction of the
computational model, we propose that the differential expression of Apelin and
APJ yields a "self-generated" gradient mechanisms that accelerates the
extension of the sprout.Comment: 48 pages, 10 figures, 8 supplementary figures. Accepted for
publication in PLoS ON
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