A Mechanogenetic Model of Exercise-Induced Pulmonary Haemorrhage in the Thoroughbred Horse

Exercise-induced pulmonary haemorrhage (EIPH) occurs in horses performing high-intensity athletic activity. The application of physics principles to derive a ‘physical model’, which is coherent with existing physiology and cell biology data, shows that critical parameters for capillary rupture are cell–cell adhesion and cell stiffness (cytoskeleton organisation). Specifically, length of fracture in the capillary is a ratio between the energy involved in cell–cell adhesion and the stiffness of cells suggesting that if the adhesion diminishes and/or that the stiffness of cells increases EIPH is more likely to occur. To identify genes associated with relevant cellular or physiological phenotypes, the physical model was used in a post-genome-wide association study (GWAS) to define gene sets associated with the model parameters. The primary study was a GWAS of EIPH where the phenotype was based on weekly tracheal wash samples collected over a two-year period from 72 horses in a flat race training yard. The EIPH phenotype was determined from cytological analysis of the tracheal wash samples, by scoring for the presence of red blood cells and haemosiderophages. Genotyping was performed using the Illumina Equine SNP50 BeadChip and analysed using linear regression in PLINK. Genes within significant genome regions were selected for sets based on their GeneOntology biological process, and analysed using fastBAT. The gene set analysis showed that genes associated with cell stiffness (cytoskeleton organisation) and blood flow have the most significant impact on EIPH risk.

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Using approximate Bayesian computation to quantify cell-cell adhesion parameters in a cell migratory process

10.1101/068791 ◽

2016 ◽

Author(s):

Robert J. H. Ross ◽

R. E. Baker ◽

Andrew Parker ◽

M. J. Ford ◽

R. L. Mort ◽

...

Keyword(s):

Cell Adhesion ◽

Approximate Bayesian Computation ◽

Cell Interactions ◽

Model Parameters ◽

Bayesian Computation ◽

Accurate Identification ◽

A Cell ◽

Approximate Bayesian ◽

Set Up ◽

Cell Cell

AbstractIn this work we implement approximate Bayesian computational methods to improve the design of a wound-healing assay used to quantify cell-cell interactions. This is important as cell-cell interactions, such as adhesion and repulsion, have been shown to play an important role in cell migration. Initially, we demonstrate with a model of an ideal experiment that we are able to identify model parameters for agent motility and adhesion, given we choose appropriate summary statistics. Following this, we replace our model of an ideal experiment with a model representative of a practically realisable experiment. We demonstrate that, given the current (and commonly used) experimental set-up, model parameters cannot be accurately identified using approximate Bayesian computation methods. We compare new experimental designs through simulation, and show more accurate identification of model parameters is possible by expanding the size of the domain upon which the experiment is performed, as opposed to increasing the number of experimental repeats. The results presented in this work therefore describe time and cost-saving alterations for a commonly performed experiment for identifying cell motility parameters. Moreover, the results presented in this work will be of interest to those concerned with performing experiments that allow for the accurate identification of parameters governing cell migratory processes, especially cell migratory processes in which cell-cell adhesion or repulsion are known to play a significant role.

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Computational Modelling of Nephron Progenitor Cell Movement and Aggregation During Kidney Organogenesis

10.21203/rs.2.22766/v1 ◽

2020 ◽

Author(s):

Pauli Tikka ◽

Moritz Mercker ◽

Ilya Skovorodkin ◽

Ulla Saarela ◽

Seppo Vainio ◽

...

Keyword(s):

Cell Adhesion ◽

Potts Model ◽

Ex Vivo ◽

Computational Modelling ◽

Cell Movement ◽

Model Parameters ◽

Cellular Potts Model ◽

Kidney Organogenesis ◽

Nephron Progenitor ◽

Cell Cell

Abstract During early kidney organogenesis, nephron progenitor (NP) cells move from the tip to the corner region of the ureteric bud (UB) branches in order to form the pretubular aggregate, the early structure giving rise to nephron formation. Chemotaxis and cell-cell adhesion differences are believed to drive cell patterning during this critical period of organogenesis, but the spatiotemporal organization of this process is incompletely understood. We applied a Cellular Potts model to explore to how these processes contribute to directed cell movement and aggregation. Model parameters were estimated based on fitting to experimental data obtained in ex vivo kidney explant and dissociation-reaggregation organoid culture studies. Our simulations indicated that optimal enrichment and aggregation of NP cells in the UB corner niche requires chemoattractant secretion from both the UB epithelial cells and the NP cells themselves, as well as differences in cell-cell adhesion energies. Furthermore, NP cells were observed, both experimentally and by modelling, to move at higher speed in the UB corner as compared to the tip region where they originated. The existence of different cell speed domains along the UB was confirmed using self-organizing map analysis. In summary, we demonstrated the suitability of a Cellular Potts Model approach to simulate cell movement and patterning during early nephrogenesis. Further refinement of the model should allow us to recapitulate the effects of developmental changes of cell phenotypes and molecular crosstalk during organ development.

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The role of spectrin in cell adhesion and cell–cell contact

Experimental Biology and Medicine ◽

10.1177/1535370219859003 ◽

2019 ◽

Vol 244 (15) ◽

pp. 1303-1312 ◽

Cited By ~ 6

Author(s):

Beata Machnicka ◽

Renata Grochowalska ◽

Dżamila M Bogusławska ◽

Aleksander F Sikorski

Keyword(s):

Extracellular Matrix ◽

Cell Adhesion ◽

Cell Surface ◽

Cell Biology ◽

Membrane Integrity ◽

Cell Contact ◽

Surface Activities ◽

New Findings ◽

Cell Cell

Spectrins are proteins that are responsible for many aspects of cell function and adaptation to changing environments. Primarily the spectrin-based membrane skeleton maintains cell membrane integrity and its mechanical properties, together with the cytoskeletal network a support cell shape. The occurrence of a variety of spectrin isoforms in diverse cellular environments indicates that it is a multifunctional protein involved in numerous physiological pathways. Participation of spectrin in cell–cell and cell–extracellular matrix adhesion and formation of dynamic plasma membrane protrusions and associated signaling events is a subject of interest for researchers in the fields of cell biology and molecular medicine. In this mini-review, we focus on data concerning the role of spectrins in cell surface activities such as adhesion, cell–cell contact, and invadosome formation. We discuss data on different adhesion proteins that directly or indirectly interact with spectrin repeats. New findings support the involvement of spectrin in cell adhesion and spreading, formation of lamellipodia, and also the participation in morphogenetic processes, such as eye development, oogenesis, and angiogenesis. Here, we review the role of spectrin in cell adhesion and cell–cell contact.Impact statementThis article reviews properties of spectrins as a group of proteins involved in cell surface activities such as, adhesion and cell–cell contact, and their contribution to morphogenesis. We show a new area of research and discuss the involvement of spectrin in regulation of cell–cell contact leading to immunological synapse formation and in shaping synapse architecture during myoblast fusion. Data indicate involvement of spectrins in adhesion and cell–cell or cell–extracellular matrix interactions and therefore in signaling pathways. There is evidence of spectrin’s contribution to the processes of morphogenesis which are connected to its interactions with adhesion molecules, membrane proteins (and perhaps lipids), and actin. Our aim was to highlight the essential role of spectrin in cell–cell contact and cell adhesion.

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