Repository logo
 

Force-based three-dimensional model predicts mechanical drivers of cell sorting.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Revell, Christopher  ORCID logo  https://orcid.org/0000-0002-9646-2888
Blumenfeld, Raphael 
Chalut, Kevin J 

Abstract

Many biological processes, including tissue morphogenesis, are driven by cell sorting. However, the primary mechanical drivers of sorting in multicellular aggregates (MCAs) remain controversial, in part because there is no appropriate computational model to probe mechanical interactions between cells. To address this important issue, we developed a three-dimensional, local force-based simulation based on the subcellular element method. In our method, cells are modelled as collections of locally interacting force-bearing elements. We use the method to investigate the effects of tension and cell-cell adhesion on MCA sorting. We predict a minimum level of adhesion to produce inside-out sorting of two cell types, which is in excellent agreement with observations in several developmental systems. We also predict the level of tension asymmetry needed for robust sorting. The generality and flexibility of the method make it applicable to tissue self-organization in a myriad of other biological processes, such as tumorigenesis and embryogenesis.

Description

Keywords

biological physics, cell sorting, cortical tension, differential interfacial tension, modelling, self-organization, Carcinogenesis, Cell Movement, Computer Simulation, Embryonic Development, Models, Biological

Journal Title

Proc Biol Sci

Conference Name

Journal ISSN

0962-8452
1471-2954

Volume Title

286

Publisher

The Royal Society
Sponsorship
Medical Research Council (MC_PC_12009)
This work was financially supported by the Medical Research Council and the Wellcome Trust. KC is a University Research Fellow of the Royal Society, which also provided financial support for this work