A Multicellular Model of Intestinal Crypt Buckling and Fission

Axel A. Almet, Barry D. Hughes, Kerry A. Landman, Inke S. Näthke, James M. Osborne (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    11 Citations (Scopus)
    360 Downloads (Pure)

    Abstract

    Crypt fission is an in vivo tissue deformation process that is involved in both intestinal homeostasis and colorectal tumourigenesis. Despite its importance, the mechanics underlying crypt fission are currently poorly understood. Recent experimental development of organoids, organ-like buds cultured from crypt stem cells in vitro, has shown promise in shedding light on crypt fission. Drawing inspiration from observations of organoid growth and fission in vivo, we develop a computational model of a deformable epithelial tissue layer. Results from in silico experiments show the stiffness of cells and the proportions of cell subpopulations affect the nature of deformation in the epithelial layer. In particular, we find that increasing the proportion of stiffer cells in the layer increases the likelihood of crypt fission occurring. This is in agreement with and helps explain recent experimental work.

    Original languageEnglish
    Pages (from-to)335-359
    Number of pages25
    JournalBulletin of Mathematical Biology
    Volume80
    Issue number2
    Early online date12 Dec 2017
    DOIs
    Publication statusPublished - Feb 2018

    Keywords

    • Cell stiffness
    • Chaste
    • Deformation
    • Epithelia
    • Organoid

    ASJC Scopus subject areas

    • General Neuroscience
    • Immunology
    • General Mathematics
    • General Biochemistry,Genetics and Molecular Biology
    • General Environmental Science
    • Pharmacology
    • General Agricultural and Biological Sciences
    • Computational Theory and Mathematics

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