scholarly journals How simple cell to cell communication rules can generate and maintain scale invariant gradients of signalling activity across a multicellular population

2020 ◽  
Author(s):  
Jack Oldham
Keyword(s):  
Thought Experiment ◽  
Cell Communication ◽  
Simple Cell ◽  
Scale Invariant ◽  
Discrete Signals ◽  
Graph Type ◽  
Signalling Molecule ◽  
Gradient Formation ◽  
Local Cell ◽  
Intuitive Method

AbstractThis paper shows computationally and conceptually how gradients of signalling activity can be generated and dynamically maintained across a population of cells using very simple cell to cell communication rules. The rules work on the basis of cells regulating their production rate of a signalling molecule according to the production rates of their immediate neighbours. Highly stable, scale invariant signalling gradients can be formed across the population, with highest rates at the centre and lowest at the periphery.The cell to cell communication behaviour that causes gradient formation is first explained in a descriptive, thought experiment type manner. It is then defined more formally using a conceptual, mathematically discrete computational model, which provides a network or graph type framework in which it is easy to analyse and control discrete signals that are sent between neighbouring cells. This provides an intuitive method of explaining how the signalling gradient emerges as a result of local cell to cell communication. Finally, examples of gradient formation are shown using software implementations of the model.

scholarly journals Quorum sensing and genomic studies of a marine bacterium Vibrio variabilis strain T01

2015 ◽  
Author(s):  
Kok-Gan Chan ◽  
Nur Izzati Mohamad
Keyword(s):  
Quorum Sensing ◽  
Coastal Waters ◽  
Marine Bacterium ◽  
Cell Communication ◽  
Whole Genome ◽  
Whole Genome Analysis ◽  
Protein Coding ◽  
Signalling Molecule ◽  
Genomic Studies ◽  
Rna Genes

Vibrio variabilis strain T01 was isolated from the coastal waters in Hulu Selangor, Malaysia and its genome sequenced. This curved gram-negative bacterium shows cell-to-cell communication properties. The characteristics of the sequenced genome and its annotation processes are described here. The finished assembled whole genome of T01T exhibits genome size of 4,529,728 bp in 83 contigs with 46.22% G+C content, 4053 protein coding genes and 94 RNA genes. The whole genome analysis revealed the presence of quorum sensing signalling molecule synthase gene (luxM) which is crucial to understand the quorum sensing dependent phenotypes in this isolate.

scholarly journals A new improved and extended version of the multicell bacterial simulator gro

2016 ◽  
Author(s):  
Martín Gutiérrez ◽  
Paula Gregorio-Godoy ◽  
Guillermo Pérez del Pulgar ◽  
Luis Muñoz ◽  
Sandra Sáez ◽  
...  
Keyword(s):  
Synthetic Biology ◽  
Timed Automata ◽  
Cell Communication ◽  
Colony Growth ◽  
Communication Process ◽  
Intercellular Signaling ◽  
Dividing Cells ◽  
A Cell ◽  
Local Cell ◽  
Cell Cell

Abstractgro is a cell programming language developed in Klavins Lab for simulating colony growth and cell-cell communication. It is used as a synthetic biology prototyping tool for simulating multicellular biocircuits. In this work, we present several extensions made to gro that improve the performance of the simulator, make it easier to use and provide new functionalities. The new version of gro is between one and two orders of magnitude faster than the original version. It is able to grow microbial colonies with up to 105 cells in less than 20 minutes. A new library, CellEngine, accelerates the resolution of spatial physical interactions between growing and dividing cells by implementing a new shoving algorithm. A genetic library, CellPro, based on Probabilistic Timed Automata, simulates gene expression dynamics using simplified and easy to compute digital proteins. We also propose a more convenient language specification layer, ProSpec, based on the idea that proteins drive cell behavior. CellNutrient, another library, implements Monod-based growth and nutrient uptake functionalities. The intercellular signaling management was improved and extended in a library called CellSignals. Finally, bacterial conjugation, another local cell-cell communication process, was added to the simulator. To show the versatility and potential outreach of this version of gro, we provide studies and novel examples ranging from synthetic biology to evolutionary microbiology. We believe that the upgrades implemented for gro have made it into a powerful and fast prototyping tool capable of simulating a large variety of systems and synthetic biology designs.

scholarly journals Intraocular dendritic cells characterize HLA-B27-associated acute anterior uveitis

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Maren Kasper ◽  
Michael Heming ◽  
David Schafflick ◽  
Xiaolin Li ◽  
Tobias Lautwein ◽  
...  
Keyword(s):  
Anterior Uveitis ◽  
Cell Communication ◽  
Leukocyte Infiltration ◽  
Hla B27 ◽  
Acute Anterior Uveitis ◽  
Immune Mediated ◽  
Single Cell Rna Sequencing ◽  
Infectious Endophthalmitis ◽  
Local Cell

Uveitis describes a heterogeneous group of inflammatory eye diseases characterized by infiltration of leukocytes into the uveal tissues. Uveitis associated with the HLA haplotype B27 (HLA-B27) is a common subtype of uveitis and a prototypical ocular immune-mediated disease. Local immune mechanisms driving human uveitis are poorly characterized mainly due to the limited available biomaterial and subsequent technical limitations. Here, we provide the first high-resolution characterization of intraocular leukocytes in HLA-B27-positive (n = 4) and -negative (n = 2) anterior uveitis and an infectious endophthalmitis control (n = 1) by combining single-cell RNA-sequencing with flow cytometry and protein analysis. Ocular cell infiltrates consisted primarily of lymphocytes in both subtypes of uveitis and of myeloid cells in infectious endophthalmitis. HLA-B27-positive uveitis exclusively featured a plasmacytoid and classical dendritic cell (cDC) infiltrate. Moreover, cDCs were central in predicted local cell-cell communication. This suggests a unique pattern of ocular leukocyte infiltration in HLA-B27-positive uveitis with relevance to DCs.

scholarly journals Engineered cell-to-cell signalling within growing bacterial cellulose pellicles

2018 ◽  
Author(s):  
Kenneth T Walker ◽  
Vivianne J Goosens ◽  
Akashaditya Das ◽  
Alicia E Graham ◽  
Tom Ellis
Keyword(s):  
Bacterial Cellulose ◽  
Cell Signalling ◽  
Polymer Network ◽  
Cell Communication ◽  
Homoserine Lactone ◽  
Structured Materials ◽  
Signalling Molecule ◽  
Synthetic Cell ◽  
Differential Gene ◽  
High Yields

AbstractBacterial cellulose is a strong and flexible biomaterial produced at high yields by Acetobacter species and has applications in healthcare, biotechnology and electronics. Naturally, bacterial cellulose grows as a large unstructured polymer network around the bacteria that produce it, and tools to enable these bacteria to respond to different locations are required to grow more complex structured materials. Here, we introduce engineered cell-to-cell communication into a bacterial cellulose-producing strain of Komagataeibacter rhaeticus to enable different cells to detect their proximity within growing material and trigger differential gene expression in response. Using synthetic biology tools, we engineer Sender and Receiver strains of K. rhaeticus to produce and respond to the diffusible signalling molecule, acyl-homoserine lactone (AHL). We demonstrate that communication can occur both within and between growing pellicles and use this in a boundary detection experiment, where spliced and joined pellicles sense and reveal their original boundary. This work sets the basis for synthetic cell-to-cell communication within bacterial cellulose and is an important step forward for pattern formation within engineered living materials.

scholarly journals Cell-to-cell communication mediates glioblastoma progression in Drosophila

Biology Open ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. bio053405
Author(s):  
Marta Portela ◽  
Teresa Mitchell ◽  
Sergio Casas-Tintó
Keyword(s):  
Brain Tissue ◽  
Cell Communication ◽  
Matrix Metalloproteases ◽  
Cellular Interactions ◽  
Jnk Pathway ◽  
Cellular Events ◽  
Signalling Molecule ◽  
The Central Nervous System ◽  
Mediate Cell ◽  
Molecular Signals

ABSTRACTGlioblastoma (GB) is the most aggressive and lethal tumour of the central nervous system (CNS). GB cells grow rapidly and display a network of projections, ultra-long tumour microtubes (TMs), that mediate cell to cell communication. GB-TMs infiltrate throughout the brain, enwrap neurons and facilitate the depletion of the signalling molecule wingless (Wg)/WNT from the neighbouring healthy neurons. GB cells establish a positive feedback loop including Wg signalling upregulation that activates cJun N-terminal kinase (JNK) pathway and matrix metalloproteases (MMPs) production, which in turn promote further TMs infiltration, GB progression and neurodegeneration. Thus, cellular and molecular signals other than primary mutations emerge as central players of GB. Using a Drosophila model of GB, we describe the temporal organisation of the main cellular events that occur in GB, including cell-to-cell interactions, neurodegeneration and TM expansion. We define the progressive activation of JNK pathway signalling in GB mediated by the receptor Grindelwald (Grnd) and activated by the ligand Eiger (Egr)/TNFα produced by surrounding healthy brain tissue. We propose that cellular interactions of GB with the healthy brain tissue precede TM expansion and conclude that non-autonomous signals facilitate GB progression. These results contribute to deciphering the complexity and versatility of these incurable tumours.

scholarly journals Glypicans define unique roles for the Hedgehog co-receptors Boi and Ihog in cytoneme-mediated gradient formation

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Eleanor Simon ◽  
Carlos Jiménez-Jiménez ◽  
Irene Seijo-Barandiarán ◽  
Gustavo Aguilar ◽  
David Sánchez-Hernández ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Direct Contact ◽  
Tissue Repair ◽  
Cell Communication ◽  
Target Cells ◽  
Signaling Proteins ◽  
Long Distance Dispersal ◽  
Long Distance ◽  
Gradient Formation ◽  
Hh Signaling

The conserved family of Hedgehog (Hh) signaling proteins plays a key role in cell-cell communication during development, tissue repair and cancer progression, inducing distinct concentration-dependent responses in target cells located at short and long distances. One simple mechanism for long distance dispersal of the lipid modified Hh is the direct contact between cell membranes through filopodia-like structures known as cytonemes. Here we have analyzed in Drosophila the interaction between the glypicans Dally and Dally-like protein, necessary for Hh signaling, and the adhesion molecules and Hh coreceptors Ihog and Boi. We describe that glypicans are required to maintain the levels of Ihog, but not of Boi. We also show that the overexpression of Ihog, but not of Boi, regulates cytoneme dynamics through their interaction with glypicans, the Ihog fibronectin III domains being essential for this interaction. Our data suggest that the regulation of glypicans over Hh signaling is specifically given by their interaction with Ihog in cytonemes. Contrary to previous data, we also show that there is no redundancy of Ihog and Boi functions in Hh gradient formation, being Ihog, but not of Boi, essential for the long-range gradient.

scholarly journals How to Assemble a Scale-Invariant Gradient

2021 ◽  
Author(s):  
Arnab Datta ◽  
Sagnik Ghosh ◽  
Jane Kondev
Keyword(s):  
Protein Concentration ◽  
Diffusion Constant ◽  
Positional Information ◽  
Yeast Cells ◽  
Scale Invariant ◽  
Linear Dimensions ◽  
Gradient Formation ◽  
A Cell ◽  
Protein Gradients ◽  
Actin Cables

Intracellular protein gradients serve a variety of functions, such as the establishment of cell polarity and to provide positional information for gene expression in developing embryos. Given that cell size in a population can vary considerably, for the protein gradients to work properly they often have to be scaled to the size of the cell. Here we examine a model of protein gradient formation within a cell that relies on cytoplasmic diffusion and cortical transport of proteins toward a cell pole. We show that the shape of the protein gradient is determined solely by the cell geometry. Furthermore, we show that the length scale over which the protein concentration in the gradient varies is determined by the linear dimensions of the cell, independent of the diffusion constant or the transport speed. This gradient provides scale-invariant positional information within a cell, which can be used for assembly of intracellular structures whose size is scaled to the linear dimensions of the cell, as was recently reported for the cytokinetic ring and actin cables in budding yeast cells.

scholarly journals Eph-mediated tyrosine phosphorylation of citron kinase controls abscission

2016 ◽  
Vol 214 (5) ◽  
pp. 555-569 ◽  
Author(s):  
Thomas Jungas ◽  
Renaud T. Perchey ◽  
Mohamad Fawal ◽  
Caroline Callot ◽  
Carine Froment ◽  
...  
Keyword(s):  
Cell Division ◽  
Tyrosine Phosphorylation ◽  
Cell Communication ◽  
Local Environment ◽  
Developing Neocortex ◽  
Citron Kinase ◽  
Local Cell ◽  
Communication Pathway

Cytokinesis is the last step of cell division, culminating in the physical separation of daughter cells at the end of mitosis. Cytokinesis is a tightly regulated process that until recently was mostly viewed as a cell-autonomous event. Here, we investigated the role of Ephrin/Eph signaling, a well-known local cell-to-cell communication pathway, in cell division. We show that activation of Eph signaling in vitro leads to multinucleation and polyploidy, and we demonstrate that this is caused by alteration of the ultimate step of cytokinesis, abscission. Control of abscission requires Eph kinase activity, and Src and citron kinase (CitK) are downstream effectors in the Eph-induced signal transduction cascade. CitK is phosphorylated on tyrosines in neural progenitors in vivo, and Src kinase directly phosphorylates CitK. We have identified the specific tyrosine residues of CitK that are phosphorylated and show that tyrosine phosphorylation of CitK impairs cytokinesis. Finally, we show that, similar to CitK, Ephrin/Eph signaling controls neuronal ploidy in the developing neocortex. Our study indicates that CitK integrates intracellular and extracellular signals provided by the local environment to coordinate completion of cytokinesis.

scholarly journals Biomechanical ordering of dense cell populations

2008 ◽  
Vol 105 (40) ◽  
pp. 15346-15351 ◽  
Author(s):  
Dmitri Volfson ◽  
Scott Cookson ◽  
Jeff Hasty ◽  
Lev S. Tsimring
Keyword(s):  
Spatial Organization ◽  
Aqueous Media ◽  
Cell Communication ◽  
Fundamental Aspect ◽  
Cell Dynamics ◽  
Bacterial Populations ◽  
Tensor Order ◽  
Local Cell ◽  
Discrete Element Simulations ◽  
The Relationship

The structure of bacterial populations is governed by the interplay of many physical and biological factors, ranging from properties of surrounding aqueous media and substrates to cell–cell communication and gene expression in individual cells. The biomechanical interactions arising from the growth and division of individual cells in confined environments are ubiquitous, yet little work has focused on this fundamental aspect of colony formation. We analyze the spatial organization of Escherichia coli growing in a microfluidic chemostat. We find that growth and expansion of a dense colony of cells leads to a dynamical transition from an isotropic disordered phase to a nematic phase characterized by orientational alignment of rod-like cells. We develop a continuum model of collective cell dynamics based on equations for local cell density, velocity, and the tensor order parameter. We use this model and discrete element simulations to elucidate the mechanism of cell ordering and quantify the relationship between the dynamics of cell proliferation and the spatial structure of the population.

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