A Multicellular Model of Intestinal Crypt Buckling and Fission

Axel A. Almet; Barry D. Hughes; Kerry A. Landman; Inke S. Näthke; James M. Osborne

doi:10.1007/s11538-017-0377-z

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)

Cell and Developmental Biology

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

309 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 language	English
Pages (from-to)	335-359
Number of pages	25
Journal	Bulletin of Mathematical Biology
Volume	80
Issue number	2
Early online date	12 Dec 2017
DOIs	https://doi.org/10.1007/s11538-017-0377-z
Publication status	Published - Feb 2018

Keywords

Cell stiffness
Chaste
Deformation
Epithelia
Organoid

ASJC Scopus subject areas

Neuroscience(all)
Immunology
Mathematics(all)
Biochemistry, Genetics and Molecular Biology(all)
Environmental Science(all)
Pharmacology
Agricultural and Biological Sciences(all)
Computational Theory and Mathematics

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10.1007/s11538-017-0377-z

Author Accepted ManuscriptAccepted author manuscript, 4.62 MB

Sonopill: Minimally Invasive Gastrointestinal Diagnosis and Therapy (Joint with University of Glasgow & Heriot Watt University)
Cochran, S., Corner, G., Cuschieri, A., Nathke, I. & Steele, B.
Engineering and Physical Sciences Research Council
27/05/13 → 14/12/18
Project: Research

Cite this

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title = "A Multicellular Model of Intestinal Crypt Buckling and Fission",

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",

author = "Almet, {Axel A.} and Hughes, {Barry D.} and Landman, {Kerry A.} and N{\"a}thke, {Inke S.} and Osborne, {James M.}",

note = "Axel A. Almet, Barry D. Hughes and Kerry A. Landman were supported by the Australian Research Council (DP110100795). Axel A. Almet and James M. Osborne were funded by a University of Melbourne ECR Grant.",

year = "2018",

month = feb,

doi = "10.1007/s11538-017-0377-z",

language = "English",

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journal = "Bulletin of Mathematical Biology",

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TY - JOUR

T1 - A Multicellular Model of Intestinal Crypt Buckling and Fission

AU - Almet, Axel A.

AU - Hughes, Barry D.

AU - Landman, Kerry A.

AU - Näthke, Inke S.

AU - Osborne, James M.

N1 - Axel A. Almet, Barry D. Hughes and Kerry A. Landman were supported by the Australian Research Council (DP110100795). Axel A. Almet and James M. Osborne were funded by a University of Melbourne ECR Grant.

PY - 2018/2

Y1 - 2018/2

N2 - 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.

AB - 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.

KW - Cell stiffness

KW - Chaste

KW - Deformation

KW - Epithelia

KW - Organoid

U2 - 10.1007/s11538-017-0377-z

DO - 10.1007/s11538-017-0377-z

M3 - Article

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SN - 0092-8240

VL - 80

SP - 335

EP - 359

JO - Bulletin of Mathematical Biology

JF - Bulletin of Mathematical Biology

IS - 2

ER -

A Multicellular Model of Intestinal Crypt Buckling and Fission

Abstract

Keywords

ASJC Scopus subject areas

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Projects

Sonopill: Minimally Invasive Gastrointestinal Diagnosis and Therapy (Joint with University of Glasgow & Heriot Watt University)

Cite this