A Multicellular Model of Intestinal Crypt Buckling and Fission

Bull Math Biol. 2018 Feb;80(2):335-359. doi: 10.1007/s11538-017-0377-z. Epub 2017 Dec 12.

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.

Keywords: Cell stiffness; Chaste; Deformation; Epithelia; Organoid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomechanical Phenomena
  • Cell Death
  • Cell Proliferation
  • Cell Size
  • Colorectal Neoplasms / etiology
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / physiopathology
  • Computer Simulation
  • Homeostasis
  • Humans
  • Intestinal Mucosa / anatomy & histology*
  • Intestinal Mucosa / pathology
  • Intestinal Mucosa / physiopathology
  • Mathematical Concepts
  • Models, Anatomic
  • Models, Biological*