Modeling the finger instability in an expanding cell monolayer

Tarle, Victoria; Ravasio, Andrea; Hakim, Vincent; Gov, Nir S.

doi:10.1039/c5ib00092k

Cited by 65 publications

(97 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In parts of the phase diagram, we observe a fingering instability [90][91][92][93] where regions a few cells wide migrate outward from the centre, as shown in Fig 6e. When τ α drops below approximately 10, we observe that the fluctuations of the boundary already present in Fig 6d become unconstrained. This is a mechanically unstable regime: Eventually, these cells will detach, a process we are not yet able to model due to the topological change that it would imply (see, Fig 3).…”

Section: Activity Driven Fluidisation Phase Diagrammentioning

confidence: 90%

Active Vertex Model for Cell-Resolution Description of Epithelial Tissue Mechanics

Barton

Henkes

Weijer

et al. 2016

Preprint

View full text Add to dashboard Cite

We introduce an Active Vertex Model (AVM) for cell-resolution studies of the mechanics of confluent epithelial tissues consisting of tens of thousands of cells, with a level of detail inaccessible to similar methods. The AVM combines the Vertex Model for confluent epithelial tissues with active matter dynamics. This introduces a natural description of the cell motion and accounts for motion patterns observed on multiple scales. Furthermore, cell contacts are generated dynamically from positions of cell centres. This not only enables efficient numerical implementation, but provides a natural description of the T1 transition events responsible for local tissue rearrangements. The AVM also includes cell alignment, cellspecific mechanical properties, cell growth, division and apoptosis. In addition, the AVM introduces a flexible, dynamically changing boundary of the epithelial sheet allowing for studies of phenomena such as the fingering instability or wound healing. We illustrate these capabilities with a number of case studies. Author summaryWe present a detailed analysis of the Active Vertex Model to study the mechanics of confluent epithelial tissues and cell monolayers. The model combines the commonly used Vertex Model for describing epithelial tissue mechanics with the active matter dynamics extensively studied in soft matter physics. We utlise an exact mathematical mapping that enables a very efficient numerical implementation using standard methods for simulating particle-based models. System sizes accessible to this model allow us to probe the dynamical motion patterns that occur in tissues over a range of length-and time-scales previously inaccessible to available simulation tools. Our model also includes a number of essential features required to properly describe actual biological systems such as cell growth, cell division and aptotsis, as well as the dynamic boundary of the epithelial sheet. This allows us to study phenomena such as the finger-like protrusions in cell monolayers and processes related to wound healing. The model is implemented into the SAMoS PLOS Computational Biology | https://doi

show abstract

Section: Activity Driven Fluidisation Phase Diagrammentioning

confidence: 90%

Active Vertex Model for Cell-Resolution Description of Epithelial Tissue Mechanics

Barton

Henkes

Weijer

et al. 2016

Preprint

View full text Add to dashboard Cite

show abstract

“…CIL implies that cells at the edge of a tissue exert the strongest substrate traction forces. The fact that cells at the edge might behave differently from cells in the tissue interior was observed not only in cell clusters that form supercells (7)(8)(9)(10)(11) and spreading tissues experiencing kenotaxis (16) but also, with leader cells at the tip of fingers guiding the closure of model wounds (29,47). Recently, it was shown that cell clusters consisting of nonchemotactic single cells can exhibit collective chemotaxis through CIL (33,35,48).…”

Section: Discussionmentioning

confidence: 99%

“…However, those macroscopic models cannot provide a conclusive description of how cells generate forces, align, divide, and maintain tissue integrity on an individual cell level. Cellular Potts or vertex models (20)(21)(22), phase field models (23)(24)(25), and particle models (26)(27)(28)(29) use a bottom-up approach instead and focus on individual cell properties. However, these models were mainly used to explore cellular flow patterns and tissue morphologies, and they…”

mentioning

confidence: 99%

Contact inhibition of locomotion determines cell–cell and cell–substrate forces in tissues

Zimmermann

Camley

Rappel

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

130

145

View full text Add to dashboard Cite

Cells organized in tissues exert forces on their neighbors and their environment. Those cellular forces determine tissue homeostasis as well as reorganization during embryonic development and wound healing. To understand how cellular forces are generated and how they can influence the tissue state, we develop a particle-based simulation model for adhesive cell clusters and monolayers. Cells are contractile, exert forces on their substrate and on each other, and interact through contact inhibition of locomotion (CIL), meaning that cell-cell contacts suppress force transduction to the substrate and propulsion forces align away from neighbors. Our model captures the traction force patterns of small clusters of nonmotile cells and larger sheets of motile Madin-Darby canine kidney (MDCK) cells. In agreement with observations in a spreading MDCK colony, the cell density in the center increases as cells divide and the tissue grows. A feedback between cell density, CIL, and cell-cell adhesion gives rise to a linear relationship between cell density and intercellular tensile stress and forces the tissue into a nonmotile state characterized by a broad distribution of traction forces. Our model also captures the experimentally observed tissue flow around circular obstacles, and CIL accounts for traction forces at the edge.contact inhibition | tissue mechanics | collective motility

show abstract

“…We have recently developed a theoretical model that describes the expansion of cellular monolayer [8], which includes a mechanism for dynamic instability of the edge propagation. This instability is driven by a positive feedback between the local convex curvature of the edge [9], and the tendency of cells along the edge to have motile forces directed outwards ( figure 1(a)).…”

Section: Introductionmentioning

confidence: 99%