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 journalArticle

2 Citations (Scopus)
214 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

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