A two−dimensional model of the colonic crypt accounting for the role of the basement membrane and pericryptal fibroblast sheath
The role of the basement membrane is vital in maintaining the integrity and structure of an epithelial layer, acting as both a mechanical support and forming the physical interface between epithelial cells and the surrounding connective tissue. The function of this membrane is explored here in the c...
| প্রধান লেখক: | , , , , , |
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| বিন্যাস: | Journal article |
| প্রকাশিত: |
Public Library of Science
2012
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| _version_ | 1826265591793582080 |
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| author | Dunn, S Appleton, P Nelson, S Näthke, I Gavaghan, D Osborne, J |
| author_facet | Dunn, S Appleton, P Nelson, S Näthke, I Gavaghan, D Osborne, J |
| author_sort | Dunn, S |
| collection | OXFORD |
| description | The role of the basement membrane is vital in maintaining the integrity and structure of an epithelial layer, acting as both a mechanical support and forming the physical interface between epithelial cells and the surrounding connective tissue. The function of this membrane is explored here in the context of the epithelial monolayer that lines the colonic crypt, test-tube shaped invaginations that punctuate the lining of the intestine and coordinate a regular turnover of cells to replenish the epithelial layer every few days. To investigate the consequence of genetic mutations that perturb the system dynamics and can lead to colorectal cancer, it must be possible to track the emerging tissue level changes that arise in the crypt. To that end, a theoretical crypt model with a realistic, deformable geometry is required. A new discrete crypt model is presented, which focuses on the interaction between cell- and tissue-level behaviour, while incorporating key subcellular components. The model contains a novel description of the role of the surrounding tissue and musculature, based upon experimental observations of the tissue structure of the crypt, which are also reported. A two-dimensional (2D) cross-sectional geometry is considered, and the shape of the crypt is allowed to evolve and deform. Simulation results reveal how the shape of the crypt may contribute mechanically to the asymmetric division events typically associated with the stem cells at the base. The model predicts that epithelial cell migration may arise due to feedback between cell loss at the crypt collar and density-dependent cell division, an hypothesis which can be investigated in a wet lab. This work forms the basis for investigation of the deformation of the crypt structure that can occur due to proliferation of cells exhibiting mutant phenotypes, experiments that would not be possible in vivo or in vitro. |
| first_indexed | 2024-03-06T20:26:05Z |
| format | Journal article |
| id | oxford-uuid:2f705a2c-5573-426c-9ac1-78d082aa8c2c |
| institution | University of Oxford |
| last_indexed | 2024-03-06T20:26:05Z |
| publishDate | 2012 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | oxford-uuid:2f705a2c-5573-426c-9ac1-78d082aa8c2c2022-03-26T12:55:26ZA two−dimensional model of the colonic crypt accounting for the role of the basement membrane and pericryptal fibroblast sheathJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2f705a2c-5573-426c-9ac1-78d082aa8c2cDepartment of Computer SciencePublic Library of Science2012Dunn, SAppleton, PNelson, SNäthke, IGavaghan, DOsborne, JThe role of the basement membrane is vital in maintaining the integrity and structure of an epithelial layer, acting as both a mechanical support and forming the physical interface between epithelial cells and the surrounding connective tissue. The function of this membrane is explored here in the context of the epithelial monolayer that lines the colonic crypt, test-tube shaped invaginations that punctuate the lining of the intestine and coordinate a regular turnover of cells to replenish the epithelial layer every few days. To investigate the consequence of genetic mutations that perturb the system dynamics and can lead to colorectal cancer, it must be possible to track the emerging tissue level changes that arise in the crypt. To that end, a theoretical crypt model with a realistic, deformable geometry is required. A new discrete crypt model is presented, which focuses on the interaction between cell- and tissue-level behaviour, while incorporating key subcellular components. The model contains a novel description of the role of the surrounding tissue and musculature, based upon experimental observations of the tissue structure of the crypt, which are also reported. A two-dimensional (2D) cross-sectional geometry is considered, and the shape of the crypt is allowed to evolve and deform. Simulation results reveal how the shape of the crypt may contribute mechanically to the asymmetric division events typically associated with the stem cells at the base. The model predicts that epithelial cell migration may arise due to feedback between cell loss at the crypt collar and density-dependent cell division, an hypothesis which can be investigated in a wet lab. This work forms the basis for investigation of the deformation of the crypt structure that can occur due to proliferation of cells exhibiting mutant phenotypes, experiments that would not be possible in vivo or in vitro. |
| spellingShingle | Dunn, S Appleton, P Nelson, S Näthke, I Gavaghan, D Osborne, J A two−dimensional model of the colonic crypt accounting for the role of the basement membrane and pericryptal fibroblast sheath |
| title | A two−dimensional model of the colonic crypt accounting for the role of the basement membrane and pericryptal fibroblast sheath |
| title_full | A two−dimensional model of the colonic crypt accounting for the role of the basement membrane and pericryptal fibroblast sheath |
| title_fullStr | A two−dimensional model of the colonic crypt accounting for the role of the basement membrane and pericryptal fibroblast sheath |
| title_full_unstemmed | A two−dimensional model of the colonic crypt accounting for the role of the basement membrane and pericryptal fibroblast sheath |
| title_short | A two−dimensional model of the colonic crypt accounting for the role of the basement membrane and pericryptal fibroblast sheath |
| title_sort | two dimensional model of the colonic crypt accounting for the role of the basement membrane and pericryptal fibroblast sheath |
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