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A simulation of epithelial sheet growth with internal signaling Mukhtar, Naba
Abstract
Epithelial-mesenchymal transition (EMT), a process in which immotile cells that line surfaces in the body become motile mesenchymal cells, plays a crucial role in major processes such as wound healing, embryo development, and cancer growth. Therefore, examining the dynamics behind individual and collective cell migration would allow for a better understanding of these processes. It has been previously observed that the protein YAP is activated by external mechanical stimuli and affects the expression and activation of the proteins E-cadherin and Rac1, which are involved in intercellular adhesion and migratory ability respectively. It has also been demonstrated that the mechanical stimulation of expanding cell sheets leads to the formation of finger-like projections and EMT, as well as quantitative differences in properties between cells near the sheet edge and cells away from it. Such cell sheets can be simulated using a Cellular Potts Model simulation. I propose an ODE model for YAP/Rac1/E-cadherin dynamics, implement it in a 2D computation of cells in a cellular Potts model, and demonstrate that the predictions are consistent with experimental observations of epithelial sheets grown on topographic features in vitro.
Item Metadata
Title |
A simulation of epithelial sheet growth with internal signaling
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Creator | |
Supervisor | |
Publisher |
University of British Columbia
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Date Issued |
2021
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Description |
Epithelial-mesenchymal transition (EMT), a process in which immotile cells that line surfaces in the body become motile mesenchymal cells, plays a crucial role in major processes such as wound healing, embryo development, and cancer growth. Therefore, examining the dynamics behind individual and collective cell migration would allow for a better understanding of these processes. It has been previously observed that the protein YAP is activated by external mechanical stimuli and affects the expression and activation of the proteins E-cadherin and Rac1, which are involved in intercellular adhesion and migratory ability respectively. It has also been demonstrated that the mechanical stimulation of expanding cell sheets leads to the formation of finger-like projections and EMT, as well as quantitative differences in properties between cells near the sheet edge and cells away from it. Such cell sheets can be simulated using a Cellular Potts Model simulation. I propose an ODE model for YAP/Rac1/E-cadherin dynamics, implement it in a 2D computation of cells in a cellular Potts model, and demonstrate that the predictions are consistent with experimental observations of epithelial sheets grown on topographic features in vitro.
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Genre | |
Type | |
Language |
eng
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Date Available |
2021-08-31
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Provider |
Vancouver : University of British Columbia Library
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Rights |
Attribution-NonCommercial-NoDerivatives 4.0 International
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DOI |
10.14288/1.0401824
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Graduation Date |
2021-05
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Campus | |
Scholarly Level |
Graduate
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Rights URI | |
Aggregated Source Repository |
DSpace
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Rights
Attribution-NonCommercial-NoDerivatives 4.0 International