Modelling the effect of subcellular mutations on the migration of cells in the colorectal crypt
Background: Many cancers arise from mutations in cells within epithelial tissues. Mutations manifesting at the subcellular level influence the structure and function of the tissue resulting in cancer. Previous work has proposed how cell level properties can lead to mutant cell invasion, but has not incorporated detailed subcellular modelling Results: We present a framework that allows the straightforward integration and simulation of SBML representations of subcellular dynamics within multiscale models of epithelial tissues. This allows us to investigate the effect of mutations in subcellular pathways on the migration of cells within the colorectal crypt. Using multiple models we find that mutations in APC, a key component in the Wnt signalling pathway, can bias neutral drift and can also cause downward invasion of mutant cells in the crypt. Conclusions: Our framework allows us to investigate how subcellular mutations, i.e. knockouts and knockdowns, affect cell-level properties and the resultant migration of cells within epithelial tissues. In the context of the colorectal crypt, we see that mutations in APC can lead directly to mutant cell invasion.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Due to technical limitations, full-text HTML conversion of this manuscript could not be completed. However, the manuscript can be downloaded and accessed as a PDF.
This is a list of supplementary files associated with this preprint. Click to download.
On 03 Mar, 2020
On 21 Jan, 2020
Received 19 Jan, 2020
On 17 Jan, 2020
On 15 Jan, 2020
Invitations sent on 15 Jan, 2020
On 14 Jan, 2020
On 14 Jan, 2020
Posted 19 Nov, 2019
On 20 Dec, 2019
Received 19 Dec, 2019
Received 29 Nov, 2019
On 20 Nov, 2019
On 16 Nov, 2019
Invitations sent on 15 Nov, 2019
On 13 Nov, 2019
On 12 Nov, 2019
On 12 Nov, 2019
On 16 Sep, 2019
Received 26 Aug, 2019
Received 26 Aug, 2019
On 21 Aug, 2019
On 21 Aug, 2019
Invitations sent on 12 Aug, 2019
On 04 Jun, 2019
On 29 May, 2019
On 29 May, 2019
On 28 May, 2019
Modelling the effect of subcellular mutations on the migration of cells in the colorectal crypt
On 03 Mar, 2020
On 21 Jan, 2020
Received 19 Jan, 2020
On 17 Jan, 2020
On 15 Jan, 2020
Invitations sent on 15 Jan, 2020
On 14 Jan, 2020
On 14 Jan, 2020
Posted 19 Nov, 2019
On 20 Dec, 2019
Received 19 Dec, 2019
Received 29 Nov, 2019
On 20 Nov, 2019
On 16 Nov, 2019
Invitations sent on 15 Nov, 2019
On 13 Nov, 2019
On 12 Nov, 2019
On 12 Nov, 2019
On 16 Sep, 2019
Received 26 Aug, 2019
Received 26 Aug, 2019
On 21 Aug, 2019
On 21 Aug, 2019
Invitations sent on 12 Aug, 2019
On 04 Jun, 2019
On 29 May, 2019
On 29 May, 2019
On 28 May, 2019
Background: Many cancers arise from mutations in cells within epithelial tissues. Mutations manifesting at the subcellular level influence the structure and function of the tissue resulting in cancer. Previous work has proposed how cell level properties can lead to mutant cell invasion, but has not incorporated detailed subcellular modelling Results: We present a framework that allows the straightforward integration and simulation of SBML representations of subcellular dynamics within multiscale models of epithelial tissues. This allows us to investigate the effect of mutations in subcellular pathways on the migration of cells within the colorectal crypt. Using multiple models we find that mutations in APC, a key component in the Wnt signalling pathway, can bias neutral drift and can also cause downward invasion of mutant cells in the crypt. Conclusions: Our framework allows us to investigate how subcellular mutations, i.e. knockouts and knockdowns, affect cell-level properties and the resultant migration of cells within epithelial tissues. In the context of the colorectal crypt, we see that mutations in APC can lead directly to mutant cell invasion.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Due to technical limitations, full-text HTML conversion of this manuscript could not be completed. However, the manuscript can be downloaded and accessed as a PDF.