Contact inhibition of locomotion and mechanical cross-talk between cell–cell and cell–substrate adhesion determine the pattern of junctional tension in epithelial cell aggregates

Coburn, Luke; López, Hender; Caldwell, Benjamin J.; Moussa, Elliott; Yap, Chloe X.; Priya, Rashmi; Noppe, Adrian; Roberts, Anthony P.; Lobaskin, Vladimir; Yap, Alpha; Neufeld, Zoltán; Gómez, Guillermo A.

doi:10.1091/mbc.e16-04-0226

“…We conclude by noting that recently there have been several interesting attempts at extending the Vertex Model description to three dimensions [85, 107–112]. While in principle possible, extending the AVM to a curved surface or making it fully three-dimensional would be quite involved.…”

Section: Resultsmentioning

confidence: 96%

Active Vertex Model for cell-resolution description of epithelial tissue mechanics

Barton

¹

,

Henkes

²

,

Weijer

³

et al. 2017

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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, cell-specific 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.

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“…We conclude by noting that recently there have been several interesting attempts at extending the Vertex Model description to three dimensions [85,[107][108][109][110][111][112]. While in principle possible, extending the AVM to a curved surface or making it fully three-dimensional would be quite involved.…”

Section: Discussionmentioning

confidence: 97%

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

Barton

¹

,

Henkes

²

,

Weijer

³

et al. 2016

Preprint

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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

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“…In this study, we found that genes that showed DNA methylation changes following clozapine treatment were enriched for the GO terms “cell substrate adhesion”, which is essential for cells to interact with their environments [29], and “cell matrix adhesion”, which is essential for cell migration, tissues organization, and differentiation [30]. Similarly, in a recent analysis of differential gene expression profiles in neurons from twins with treatment-resistant SCZ who had discordant responses to clozapine using pluripotent stem (iPS) cell based technology, we found that differentially expressed genes were enriched for “cell adhesion” and “biological adhesion” [6].…”

Section: Discussionmentioning

confidence: 99%

Effect of Clozapine on DNA Methylation in Peripheral Leukocytes from Patients with Treatment-Resistant Schizophrenia

Kinoshita

¹

,

Numata

²

,

Tajima

³

et al. 2017

IJMS

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Abstract:Clozapine is an atypical antipsychotic, that is established as the treatment of choice for treatment-resistant schizophrenia (SCZ). To date, no study investigating comprehensive DNA methylation changes in SCZ patients treated with chronic clozapine has been reported. The purpose of the present study is to reveal the effects of clozapine on DNA methylation in treatment-resistant SCZ. We conducted a genome-wide DNA methylation profiling in peripheral leukocytes (485,764 CpG dinucleotides) from treatment-resistant SCZ patients treated with clozapine (n = 21) in a longitudinal study. Significant changes in DNA methylation were observed at 29,134 sites after one year of treatment with clozapine, and these genes were enriched for "cell substrate adhesion" and "cell matrix adhesion" gene ontology (GO) terms. Furthermore, DNA methylation changes in the CREBBP (CREB binding protein) gene were significantly correlated with the clinical improvements. Our findings provide insights into the action of clozapine in treatment-resistant SCZ.

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Contact inhibition of locomotion and mechanical cross-talk between cell–cell and cell–substrate adhesion determine the pattern of junctional tension in epithelial cell aggregates

Cited by 23 publications

References 73 publications

Active Vertex Model for cell-resolution description of epithelial tissue mechanics

Active Vertex Model for cell-resolution description of epithelial tissue mechanics

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

Effect of Clozapine on DNA Methylation in Peripheral Leukocytes from Patients with Treatment-Resistant Schizophrenia

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