scholarly journals A Force Based Model of Individual Cell Migration With Discrete Attachment Sites and Random Switching Terms

2013 ◽  
Vol 135 (7) ◽  
Author(s):  
J. C. Dallon ◽  
Matthew Scott ◽  
W. V. Smith
Keyword(s):  
Cell Migration ◽  
Individual Cell ◽  
Cell Types ◽  
Cell Binding ◽  
Stochastic Nature ◽  
Attachment Sites ◽  
Random Switching ◽  
Cell Motion ◽  
Cellular Forces ◽  
Insight Into

A force based model of cell migration is presented which gives new insight into the importance of the dynamics of cell binding to the substrate. The main features of the model are the focus on discrete attachment dynamics, the treatment of the cellular forces as springs, and an incorporation of the stochastic nature of the attachment sites. One goal of the model is to capture the effect of the random binding and unbinding of cell attachments on global cell motion. Simulations reveal one of the most important factor influencing cell speed is the duration of the attachment to the substrate. The model captures the correct velocity and force relationships for several cell types.

scholarly journals Inferring single-cell behaviour from large-scale epithelial sheet migration patterns

2017 ◽  
Vol 14 (130) ◽  
pp. 20170147 ◽  
Author(s):  
Rachel M. Lee ◽  
Haicen Yue ◽  
Wouter-Jan Rappel ◽  
Wolfgang Losert
Keyword(s):  
Cell Migration ◽  
Large Scale ◽  
Collective Motion ◽  
Individual Cell ◽  
Metastatic Cancer ◽  
Emergent Properties ◽  
Collective Migration ◽  
Cell Behaviour ◽  
Cell Motion ◽  
Insight Into

Cell migration plays an important role in a wide variety of biological processes and can incorporate both individual cell motion and collective behaviour. The emergent properties of collective migration are receiving increasing attention as collective motion's role in diseases such as metastatic cancer becomes clear. Yet, how individual cell behaviour influences large-scale, multi-cell collective motion remains unclear. In this study, we provide insight into the mechanisms behind collective migration by studying cell migration in a spreading monolayer of epithelial MCF10A cells. We quantify migration using particle image velocimetry and find that cell groups have features of motion that span multiple length scales. Comparing our experimental results to a model of collective cell migration, we find that cell migration within the monolayer can be affected in qualitatively different ways by cell motion at the boundary, yet it is not necessary to introduce leader cells at the boundary or specify other large-scale features to recapitulate this large-scale phenotype in simulations. Instead, in our model, collective motion can be enhanced by increasing the overall activity of the cells or by giving the cells a stronger coupling between their motion and polarity. This suggests that investigating the activity and polarity persistence of individual cells will add insight into the collective migration phenotypes observed during development and disease.

scholarly journals Generation of fluorescent cell-derived-matrix to study 3D cell migration

2019 ◽  
Author(s):  
Amélie Luise Godeau ◽  
Hélène Delanoë-Ayari ◽  
Daniel Riveline
Keyword(s):  
Cell Migration ◽  
Flat Surfaces ◽  
Polymeric Networks ◽  
Motile Cells ◽  
Matrix Deformation ◽  
3D Cell Migration ◽  
Cell Motion ◽  
Cellular Forces

AbstractCell migration is involved in key phenomena in biology, ranging from development to cancer. Fibroblasts move between organs in 3D polymeric networks. So far, motile cells were mainly tracked in vitro on Petri dishes or on coverslips, i.e. 2D flat surfaces, which made the extrapolation to 3D physiological environments difficult. We therefore prepared 3D Cell Derived Matrix (CDM) with specific characteristics with the goal of extracting the main readouts required to measure and characterise cell motion: cell specific matrix deformation through the tracking of fluorescent fibronectin within CDM, focal contacts as the cell anchor and acto-myosin cytoskeleton which applies cellular forces. We report our method for generating this assay of physiological-like gel with relevant readouts together with its potential impact in explaining cell motility in vivo.

scholarly journals Accumulation of PDGF B and cell-binding forms of PDGF A in the extracellular matrix.

1993 ◽  
Vol 121 (5) ◽  
pp. 1153-1163 ◽  
Author(s):  
J L Kelly ◽  
A Sánchez ◽  
G S Brown ◽  
C N Chesterman ◽  
M J Sleigh
Keyword(s):  
Matrix Material ◽  
Cell Types ◽  
Cell Binding ◽  
Laser Confocal Microscopy ◽  
Primary Transcript ◽  
Matrix Deposition ◽  
Cell Extracts ◽  
Binding Forms ◽  
Attachment Sites ◽  
The Matrix

PDGF is a powerful mitogen initially identified within platelets, but also shown to be produced by a wide variety of cell types. PDGF is encoded on two separate genes. These give rise to three polypeptides, PDGF B and two forms of PDGF A (SA and LA), resulting from alternative splicing of the PDGF A gene primary transcript. We report that in CHO cells transfected with PDGF gene constructs and producing moderate levels of PDGF homodimers, much of the PDGF LA and B produced, but little if any SA, is found in the matrix laid down beneath the cells. Immunoreactive PDGF in cells, and in matrix below expressing cells, was visualized by laser confocal microscopy. Western blotting of protein in matrix extracts, cell extracts, and secreted into the growth medium was used to demonstrate that the range of PDGF A polypeptides seen in the matrix was overlapping with those reported previously to be cell associated in cell types such as NIH3T3 and COS 7. This suggests that attachment to matrix or cell surface may be alternative fates for these polypeptides, with fate dependent on the characteristics of the producing cells. Immunoreactive PDGF A and B could be partially released by incubation of matrix material with heparin but not with other glycosaminoglycans. Digestion of matrix with chondroitin ABC lyase but not heparitinase or collagenase displaced some PDGF from its attachment sites. The results indicate attachment of PDGF to matrix proteoglycans, at least partly through the glycosaminoglycan moieties, and perhaps to additional components. The significance of matrix deposition for PDGF action is discussed.

scholarly journals Inhibition of Vesicular Secretion in Both Neuronal and Nonneuronal Cells by a Retargeted Endopeptidase Derivative ofClostridium botulinum Neurotoxin Type A

2000 ◽  
Vol 68 (5) ◽  
pp. 2587-2593 ◽  
Author(s):  
John A. Chaddock ◽  
John R. Purkiss ◽  
Lorna M. Friis ◽  
Janice D. Broadbridge ◽  
Michael J. Duggan ◽  
...  
Keyword(s):  
Neurotransmitter Release ◽  
Botulinum Neurotoxin ◽  
Type A ◽  
Cell Types ◽  
Snare Complex ◽  
Cell Binding ◽  
Vesicle Docking ◽  
Botulinum Neurotoxin Type A ◽  
Clostridial Neurotoxins ◽  
Dose Dependent

ABSTRACT Clostridial neurotoxins potently and specifically inhibit neurotransmitter release in defined cell types by a mechanism that involves cleavage of specific components of the vesicle docking/fusion complex, the SNARE complex. A derivative of the type A neurotoxin fromClostridium botulinum (termed LHN/A) that retains catalytic activity can be prepared by proteolysis. The LHN/A, however, lacks the putative native binding domain (HC) of the neurotoxin and is thus unable to bind to neurons and effect inhibition of neurotransmitter release. Here we report the chemical conjugation of LHN/A to an alternative cell-binding ligand, wheat germ agglutinin (WGA). When applied to a variety of cell lines, including those that are ordinarily resistant to the effects of neurotoxin, WGA-LHN/A conjugate potently inhibits secretory responses in those cells. Inhibition of release is demonstrated to be ligand mediated and dose dependent and to occur via a mechanism involving endopeptidase-dependent cleavage of the natural botulinum neurotoxin type A substrate. These data confirm that the function of the HC domain of C. botulinumneurotoxin type A is limited to binding to cell surface moieties. The data also demonstrate that the endopeptidase and translocation functions of the neurotoxin are effective in a range of cell types, including those of nonneuronal origin. These observations lead to the conclusion that a clostridial endopeptidase conjugate that can be used to investigate SNARE-mediated processes in a variety of cells has been successfully generated.

scholarly journals Cancer Cell Invasion of Brain Tissue: Guided by a Prepattern?

2005 ◽  
Vol 6 (1) ◽  
pp. 21-31 ◽  
Author(s):  
Michael Wurzel ◽  
Carlo Schaller ◽  
Matthias Simon ◽  
Andreas Deutsch
Keyword(s):  
Lattice Gas ◽  
Individual Cell ◽  
Physical Structure ◽  
Tumour Cells ◽  
Malignant Cells ◽  
Malignant Brain Tumour ◽  
Tumour Bulk ◽  
Cell Motion ◽  
The Brain ◽  
Global Growth

The malignant brain tumourGlioblastoma multiforme(GBM) displays a highly invasive behaviour. Spreading of the malignant cells appears to be guided by the white matter fibre tracts within the brain. In order to understand the global growth process we introduce a lattice-gas cellular automaton model which describes the local interaction between individual malignant cells and their neighbourhood. We consider interactions between cells (brain cells and tumour cells) and between malignant cells and the fibre tracts in the brain, which are considered as a prepattern. The prepattern implies persistent individual cell motion along the fibre structure. Simulations with the model show that only the inclusion of the prepattern results in invading tumour and growing tumour islets in front of the expanding tumour bulk (i.e. the growth pattern observed in clinical practice). Our results imply that the infiltrative growth of GBMs is, in part, determined by the physical structure of the surrounding brain rather than by intrinsic properties of the tumour cells.

Nanotopography-Modulated Epithelial Cell Collective Migration

2021 ◽  
Vol 17 (6) ◽  
pp. 1079-1087
Author(s):  
Zaozao Chen ◽  
Qiwei Li ◽  
Shihui Xu ◽  
Jun Ouyang ◽  
Hongmei Wei
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Epithelial Cells ◽  
Leading Edge ◽  
Cell Types ◽  
Protein Kinase Activity ◽  
Migration Behavior ◽  
Collective Migration ◽  
Epithelial Migration ◽  
Activity Dependent

Matrix nanotopography plays an essential role in regulating cell behaviors including cell proliferation, differentiation, and migration. While studies on isolated single cell migration along the nanostructural orientation have been reported for various cell types, there remains a lack of understanding of how nanotopography regulates the behavior of collectively migrating cells during processes such as epithelial wound healing. We demonstrated that collective migration of epithelial cells was promoted on nanogratings perpendicular to, but not on those parallel to, the wound-healing axis. We further discovered that nanograting-modulated epithelial migration was dominated by the adhesion turnover process, which was Rho-associated protein kinase activity-dependent, and the lamellipodia protrusion at the cell leading edge, which was Rac1-GTPase activity-dependent. This work provides explanations to the distinct migration behavior of epithelial cells on nanogratings, and indicates that the effect of nanotopographic modulations on cell migration is cell-type dependent and involves complex mechanisms

scholarly journals Single Cell Atlas of Human Dura Reveals Cellular Meningeal Landscape and Insights into Meningioma Immune Response

2021 ◽  
Author(s):  
Anthony Z Wang ◽  
Jay Bowman-Kirigin ◽  
Rupen Desai ◽  
Pujan Patel ◽  
Bhuvic Patel ◽  
...  
Keyword(s):  
Single Cell ◽  
Immune Cell ◽  
Immune Surveillance ◽  
Copy Number Variant ◽  
Cell Types ◽  
Cell Receptor ◽  
Immune Microenvironment ◽  
Clinical Models ◽  
Insight Into

Recent investigation of the meninges, specifically the dura layer, has highlighted its importance in CNS immune surveillance beyond a purely structural role. However, most of our understanding of the meninges stems from the use of pre-clinical models rather than human samples. In this study, we use single cell RNA-sequencing to perform the first characterization of both non-tumor-associated human dura and meningioma samples. First, we reveal a complex immune microenvironment in human dura that is transcriptionally distinct from that of meningioma. In addition, through T cell receptor sequencing, we show significant TCR overlap between matched dura and meningioma samples. We also identify a functionally heterogeneous population of non-immune cell types and report copy-number variant heterogeneity within our meningioma samples. Our comprehensive investigation of both the immune and non-immune cell landscapes of human dura and meningioma at a single cell resolution provide new insight into previously uncharacterized roles of human dura.

scholarly journals eQTL Catalogue: a compendium of uniformly processed human gene expression and splicing QTLs

2020 ◽  
Author(s):  
Nurlan Kerimov ◽  
James D Hayhurst ◽  
Kateryna Peikova ◽  
Jonathan R Manning ◽  
Peter Walter ◽  
...  
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Cell Types ◽  
Summary Statistics ◽  
Ensembl Genome Browser ◽  
Cell Type Specific ◽  
Trait Locus ◽  
Rest Api ◽  
Complex Human Traits ◽  
Insight Into

An increasing number of gene expression quantitative trait locus (eQTL) studies have made summary statistics publicly available, which can be used to gain insight into complex human traits by downstream analyses, such as fine mapping and colocalisation. However, differences between these datasets, in their variants tested, allele codings, and in the transcriptional features quantified, are a barrier to their widespread use. Consequently, target genes for most GWAS signals have still not been identified. Here, we present the eQTL Catalogue (https://www.ebi.ac.uk/eqtl/), a resource which contains quality controlled, uniformly re-computed QTLs from 21 eQTL studies. We find that for matching cell types and tissues, the eQTL effect sizes are highly reproducible between studies, enabling the integrative analysis of these data. Although most cis-eQTLs were shared between most bulk tissues, the analysis of purified cell types identified a greater diversity of cell-type-specific eQTLs, a subset of which also manifested as novel disease colocalisations. Our summary statistics can be downloaded by FTP, accessed via a REST API, and visualised on the Ensembl genome browser. New datasets will continuously be added to the eQTL Catalogue, enabling the systematic interpretation of human GWAS associations across many cell types and tissues.

scholarly journals Therapeutic Exosomes in Prognosis and Developments of Coronary Artery Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Ai-Qun Chen ◽  
Xiao-Fei Gao ◽  
Zhi-Mei Wang ◽  
Feng Wang ◽  
Shuai Luo ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Cell Types ◽  
Biological Functions ◽  
Stent Restenosis ◽  
Artery Disease ◽  
Almost All ◽  
Different Cell Types ◽  
Insight Into ◽  
Systematic Knowledge

Exosomes, with an diameter of 30~150 nm, could be released from almost all types of cells, which contain diverse effective constituent, such as RNAs, proteins, lipids, and so on. In recent years, exosomes have been verified to play an important role in mechanism, diagnosis, treatment, and prognosis of cardiovascular disease, especially coronary artery disease (CAD). Moreover, it has also been shown that exosomes derived from different cell types have various biological functions based on the cell stimulation and microenvironment. However, therapeutic exosomes are currently far away from clinical translation, despite it is full of hope. In this review, we summarize an update of the recent studies and systematic knowledge of therapeutic exosomes in atherosclerosis, myocardial infarction, and in-stent restenosis, which might provide a novel insight into the treatment of CAD and promote the potential clinical application of therapeutic exosomes.

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