Modelling the effect of subcellular mutations on the migration of cells in the colorectal crypt

Romijn, Lotte B.; Almet, Axel A.; Tan, Chin Wee; Osborne, James M.

doi:10.1186/s12859-020-3391-3

Cited by 5 publications

(9 citation statements)

References 57 publications

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“…SBML and CellML have largely solved this problem in the context of reaction kinetics, and have associated APIs and model repositories, but have limited functionality for spatial models; some initiatives are ongoing in this area, such as the MultiCellML project. Many multicellular tools have support for SBML specification of subcellular processes, for example, CompuCell3D (Swat et al, 2012), Chaste (Romijn et al, 2020), and Morpheus (Starruß et al, 2014). Another aspect of this is separating out the definition of the biological process from the definition of any in silico experiments or perturbations, allowing easier comparison of model behavior with experimental data.…”

Section: Challenge 6: Data/code Standards and Benchmarksmentioning

confidence: 99%

Seven challenges in the multiscale modeling of multicellular tissues

Fletcher

Osborne

2021

WIREs Mechanisms of Disease

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The growth and dynamics of multicellular tissues involve tightly regulated and coordinated morphogenetic cell behaviors, such as shape changes, movement, and division, which are governed by subcellular machinery and involve coupling through short-and long-range signals. A key challenge in the fields of developmental biology, tissue engineering and regenerative medicine is to understand how relationships between scales produce emergent tissue-scale behaviors. Recent advances in molecular biology, live-imaging and ex vivo techniques have revolutionized our ability to study these processes experimentally. To fully leverage these techniques and obtain a more comprehensive understanding of the causal relationships underlying tissue dynamics, computational modeling approaches are increasingly spanning multiple spatial and temporal scales, and are coupling cell shape, growth, mechanics, and signaling. Yet such models remain challenging: modeling at each scale requires different areas of technical skills, while integration across scales necessitates the solution to novel mathematical and computational problems. This review aims to summarize recent progress in multiscale modeling of multicellular tissues and to highlight ongoing challenges associated with the construction, implementation, interrogation, and validation of such models.

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Section: Challenge 6: Data/code Standards and Benchmarksmentioning

confidence: 99%

Seven challenges in the multiscale modeling of multicellular tissues

Fletcher

Osborne

2021

WIREs Mechanisms of Disease

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“…Furthermore, unlike cellular automata models, cell division leads only to local topological changes. The VT model has been used to represent cellular dynamics in colonic and intestinal crypts, including for models of invasion (Mirams et al, 2012;Romijn et al, 2020). Other tissue models, such as the vertex model (Farhadifar et al, 2007), could also be appropriate for our purposes.…”

Section: Epithelial Structure and Dynamicsmentioning

confidence: 99%

Cooperative success in epithelial public goods games

Renton

Page

2021

Journal of Theoretical Biology

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Cancer cells obtain mutations which rely on the production of diffusible growth factors to confer a fitness benefit. These mutations can be considered cooperative, and studied as public goods games within the framework of evolutionary game theory. The population structure, benefit function and update rule all influence the evolutionary success of cooperators. We model the evolution of cooperation in epithelial cells using the Voronoi tessellation model. Unlike traditional evolutionary graph theory, this allows us to implement global updating, for which birth and death events are spatially decoupled. We compare, for a sigmoid benefit function, the conditions for cooperation to be favoured and/or beneficial for wellmixed and structured populations. We find that when population structure is combined with global updating, cooperation is more successful than if there were local updating or the population were well-mixed. Interestingly, the qualitative behaviour for the well-mixed population and the Voronoi tessellation model is remarkably similar, but the latter case requires significantly lower incentives to ensure cooperation.

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“…Over the following decades OS models have become more sophisticated, expanding to three dimensions and incorporating more specific subcellular information [23][24][25]. A common approach to multiscale OS models of epithelia is the inclusion of a subcellular ODE model for each cell [26]. For the epidermis, this approach has been used to investigate the role of TGF-β (transforming growth factor β: a signalling molecular thought to help regulate division and differentiation) in wound healing using a mass action model [23,24].…”

Section: Multiscale Models Of the Epidermismentioning

confidence: 99%

Multiscale modelling of desquamation in the interfollicular epidermis

Miller¹,

Crampin²,

Osborn³

2021

Preprint

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Maintenance of epidermal thickness is critical to the barrier function of the skin. Decreased tissue thickness, specifically in the stratum corneum (the outermost layer of the tissue), causes discomfort and inflammation, and is related to several severe diseases of the tissue. In order to maintain both stratum corneum thickness and overall tissue thickness it is necessary for the system to balance cell proliferation and cell loss. Cell proliferation in the epidermis occurs in the basal layer and causes constant upwards movement in the tissue. Cell loss occurs when dead cells at the top of the tissue are lost to the environment through a process called desquamation. Desquamation is thought to occur through a gradual reduction in adhesion between cells, due to the cleaving of adhesion proteins by enzymes, in the stratum corneum.In this paper we will investigate combining a (mass action) subcellular model of desquamation with a three dimensional (cell centre based) multicellular model of the interfollicular epidermis to better understand maintenance of epidermal thickness. These investigations show that hypothesised biological models for the degradation of cell-cell adhesion from the literature are able to provide a consistent rate of cell loss in the multicellular model. This loss balances proliferation, and hence maintains a homeostatic tissue thickness. Moreover, we find that multiple proliferative cell populations in the basal layer can be represented by a single proliferative cell population, simplifying investigations with this model.The model is used to investigate a disorder (Netherton Syndrome) which disrupts desquamation. The model shows how biochemical changes can cause disruptions to the tissue, resulting in a reduced tissue thickness and consequently diminishing the protective role of the tissue. A hypothetical treatment result is also investigated. Specifically, we compare the cases of a partially effective homogeneous treatment (where all cells partially recover) and a totally effective heterogeneous treatment (in which a

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Modelling the effect of subcellular mutations on the migration of cells in the colorectal crypt

Cited by 5 publications

References 57 publications

Seven challenges in the multiscale modeling of multicellular tissues

Seven challenges in the multiscale modeling of multicellular tissues

Cooperative success in epithelial public goods games

Multiscale modelling of desquamation in the interfollicular epidermis

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