8,884 research outputs found
A modelling approach towards Epidermal homoeostasis control
In order to grasp the features arising from cellular discreteness and
individuality, in large parts of cell tissue modelling agent-based models are
favoured. The subclass of off-lattice models allows for a physical motivation
of the intercellular interaction rules. We apply an improved version of a
previously introduced off-lattice agent-based model to the steady-state flow
equilibrium of skin. The dynamics of cells is determined by conservative and
drag forces,supplemented with delta-correlated random forces. Cellular
adjacency is detected by a weighted Delaunay triangulation. The cell cycle time
of keratinocytes is controlled by a diffusible substance provided by the
dermis. Its concentration is calculated from a diffusion equation with
time-dependent boundary conditions and varying diffusion coefficients. The
dynamics of a nutrient is also taken into account by a reaction-diffusion
equation. It turns out that the analysed control mechanism suffices to explain
several characteristics of epidermal homoeostasis formation. In addition, we
examine the question of how {\em in silico} melanoma with decreased basal
adhesion manage to persist within the steady-state flow-equilibrium of the
skin.Interestingly, even for melanocyte cell cycle times being substantially
shorter than for keratinocytes, tiny stochastic effects can lead to completely
different outcomes. The results demonstrate that the understanding of initial
states of tumour growth can profit significantly from the application of
off-lattice agent-based models in computer simulations.Comment: 23 pages, 7 figures, 1 table; version that is to appear in Journal of
Theoretical Biolog
Modeling and Inferring Cleavage Patterns in Proliferating Epithelia
The regulation of cleavage plane orientation is one of the key mechanisms driving
epithelial morphogenesis. Still, many aspects of the relationship between local
cleavage patterns and tissue-level properties remain poorly understood. Here we
develop a topological model that simulates the dynamics of a 2D proliferating
epithelium from generation to generation, enabling the exploration of a wide
variety of biologically plausible cleavage patterns. We investigate a spectrum
of models that incorporate the spatial impact of neighboring cells and the
temporal influence of parent cells on the choice of cleavage plane. Our findings
show that cleavage patterns generate “signature” equilibrium
distributions of polygonal cell shapes. These signatures enable the inference of
local cleavage parameters such as neighbor impact, maternal influence, and
division symmetry from global observations of the distribution of cell shape.
Applying these insights to the proliferating epithelia of five diverse
organisms, we find that strong division symmetry and moderate neighbor/maternal
influence are required to reproduce the predominance of hexagonal cells and low
variability in cell shape seen empirically. Furthermore, we present two distinct
cleavage pattern models, one stochastic and one deterministic, that can
reproduce the empirical distribution of cell shapes. Although the proliferating
epithelia of the five diverse organisms show a highly conserved cell shape
distribution, there are multiple plausible cleavage patterns that can generate
this distribution, and experimental evidence suggests that indeed plants and
fruitflies use distinct division mechanisms
Multiscale modeling of layer formation in epidermis
The mammalian skin epidermis is a stratified epithelium composed of multiple layers of epithelial cells that exist in appropriate sizes and proportions, and with distinct boundaries separating each other. How the epidermis develops from a single layer of committed precursor cells to form a complex multilayered structure of multiple cell types remains elusive. Here, we construct stochastic, three-dimensional, and multiscale models consisting of a lineage of multiple cell types to study the control of epidermal development. Symmetric and asymmetric cell divisions, stochastic cell fate transitions within the lineage, extracellular morphogens, cell-to-cell adhesion forces, and cell signaling are included in model. A GPU algorithm was developed and implemented to accelerate the simulations. These simulations show that a balance between cell proliferation and differentiation during lineage progression is crucial for the development and maintenance of the epidermal tissue. We also find that selective intercellular adhesion is critical to sharpening the boundary between layers and to the formation of a highly ordered structure. The long-range action of a morphogen provides additional feedback regulations, enhancing the robustness of overall layer formation. Our model is built upon previous experimental findings revealing the role of Ovol transcription factors in regulating epidermal development. Direct comparisons of experimental and simulation perturbations show remarkable consistency. Taken together, our results highlight the major determinants of a well-stratified epidermis: balanced proliferation and differentiation, and a combination of both short- (symmetric/asymmetric division and selective cell adhesion) and long-range (morphogen) regulations. These underlying principles have broad implications for other developmental or regenerative processes leading to the formation of multilayered tissue structures, as well as for pathological processes such as epidermal wound healing
SciTech News Volume 71, No. 2 (2017)
Columns and Reports From the Editor 3
Division News Science-Technology Division 5 Chemistry Division 8 Engineering Division 9 Aerospace Section of the Engineering Division 12 Architecture, Building Engineering, Construction and Design Section of the Engineering Division 14
Reviews Sci-Tech Book News Reviews 16
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Multi-scale model suggests the trade-off between protein and ATP demand as a driver of metabolic changes during yeast replicative ageing
The accumulation of protein damage is one of the major drivers of replicative ageing, describing a cell’s reduced ability to reproduce over time even under optimal conditions. Reactive oxygen and nitrogen species are precursors of protein damage and therefore tightly linked to ageing. At the same time, they are an inevitable by-product of the cell’s metabolism. Cells are able to sense high levels of reactive oxygen and nitrogen species and can subsequently adapt their metabolism through gene regulation to slow down damage accumulation. However, the older or damaged a cell is the less flexibility it has to allocate enzymes across the metabolic network, forcing further adaptions in the metabolism. To investigate changes in the metabolism during replicative ageing, we developed an multi-scale mathematical model using budding yeast as a model organism. The model consists of three interconnected modules: a Boolean model of the signalling network, an enzyme-constrained flux balance model of the central carbon metabolism and a dynamic model of growth and protein damage accumulation with discrete cell divisions. The model can explain known features of replicative ageing, like average lifespan and increase in generation time during successive division, in yeast wildtype cells by a decreasing pool of functional enzymes and an increasing energy demand for maintenance. We further used the model to identify three consecutive metabolic phases, that a cell can undergo during its life, and their influence on the replicative potential, and proposed an intervention span for lifespan control
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