Fletcher, A.G., Murray, P.J. and Maini, P.K. (2015) Multiscale modelling of intestinal crypt organization and carcinogenesis. Mathematical Models and Methods in Applied Sciences , 25 (13). pp. 2563-2585. ISSN 0218-2025
Abstract
Colorectal cancers are the third most common type of cancer. They originate from intestinal crypts, glands that descend from the intestinal lumen into the underlying connective tissue. Normal crypts are thought to exist in a dynamic equilibrium where the rate of cell production at the base of a crypt is matched by that of loss at the top. Understanding how genetic alterations accumulate and proceed to disrupt this dynamic equilibrium is fundamental to understanding the origins of colorectal cancer. Colorectal cancer emerges from the interaction of biological processes that span several spatial scales, from mutations that cause inappropriate intracellular responses to changes at the cell/tissue level, such as uncontrolled proliferation and altered motility and adhesion. Multiscale mathematical modelling can provide insight into the spatiotemporal organisation of such a complex, highly regulated and dynamic system. Moreover, the aforementioned challenges are inherent to the multiscale modelling of biological tissue more generally. In this review we describe the mathematical approaches that have been applied to investigate multiscale aspects of crypt behavior, highlighting a number of model predictions that have since been validated experimentally. We also discuss some of the key mathematical and computational challenges associated with the multiscale modelling approach. We conclude by discussing recent efforts to derive coarse-grained descriptions of such models, which may offer one way of reducing the computational cost of simulation by leveraging well-established tools of mathematical analysis to address key problems in multiscale modelling.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2015 World Scientific Publishing. This is an author produced version of a paper subsequently published in Mathematical Models and Methods in Applied Sciences. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Off-lattice models; continuum models; multiscale models; coarse-graining; intestine; colorectal cancer |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Mathematics and Statistics (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 15 Feb 2016 14:16 |
Last Modified: | 22 Jul 2017 23:38 |
Published Version: | http://dx.doi.org/10.1142/S0218202515400187 |
Status: | Published |
Publisher: | World Scientific Publishing |
Identification Number: | 10.1142/S0218202515400187 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:94917 |