scholarly journals Semblance of heterogeneity in collective cell migration

2017 ◽  
Author(s):  
Linus J. Schumacher ◽  
Philip K. Maini ◽  
Ruth E. Baker

AbstractCell population heterogeneity is increasingly a focus of inquiry in biological research. For example, cell migration studies have investigated the heterogeneity of invasiveness and taxis in development, wound healing, and cancer. However, relatively little effort has been devoted to explore when heterogeneity is mechanistically relevant and how to reliably measure it. Statistical methods from the animal movement literature offer the potential to analyse heterogeneity in collections of cell tracking data. A popular measure of heterogeneity, which we use here as an example, is the distribution of delays in directional cross-correlation. Employing a suitably generic, yet minimal, model of collective cell movement in three dimensions, we show how using such measures to quantify heterogeneity in tracking data can result in the inference of heterogeneity where there is none. Our study highlights a potential pitfall in the statistical analysis of cell population heterogeneity, and we argue this can be mitigated by the appropriate choice of null models.Highlightsgroups of identical cells appear heterogeneous due to limited sampling and experimental repeatabilityheterogeneity bias increases with attraction/repulsion between cellsmovement in confined environments decreases apparent heterogeneityhypothetical applications in neural crest and in vitro cancer systemsIn BriefWe use a mathematical model to show how cell populations can appear heterogeneous in their migratory characteristics, even though they are made up of identically-behaving individual cells. This has important consequences for the study of collective cell migration in areas such as embryo development or cancer invasion.

2019 ◽  
Author(s):  
Juan S. Vargas Soto ◽  
Rowshyra A. Castañeda ◽  
Nicholas E. Mandrak ◽  
Péter K. Molnár

AbstractRemote detectors are being used increasingly often to study aquatic and aerial species, for which movement is significantly different from terrestrial species. While terrestrial camera-trapping studies have shown that capture frequency, along with the species’ movement speed and detector specifications can be used to estimate absolute densities, the approach has not yet been adapted to cases where movement occurs in three dimensions. Frameworks based on animal movement patterns allow estimating population density from camera-trapping data when animals are not individually distinguishable.Here we adapt one such framework to three-dimensional movement to characterize the relationship between population density, animal speed, characteristics of a remote sensor’s detection zone, and detection frequency. The derivation involves defining the detection zone mathematically and calculating the mean area of the profile it presents to approaching individuals.We developed two variants of the model – one assuming random movement of all individuals, and one allowing for different probabilities for each approach direction (e.g. that animals more often swim/fly horizontally than vertically). We used computer simulations to evaluate model performance for a wide range of animal and detector densities. Simulations show that in ideal conditions the method approximates true density well, and that estimates become increasingly accurate using more detectors, or sampling for longer. Moreover, the method is robust to invalidation of assumptions, accuracy is decreased only in extreme cases where all detectors are facing the same way.We provide equations for estimating population density from detection frequency and outline how to estimate the necessary parameters. We discuss how environmental variables and species-specific characteristics affect parameter estimates and how to account for these differences in density estimations.Our method can be applied to common remote detection methods (cameras and acoustic detectors), which are currently being used to study a diversity of species and environments. Therefore, our work may significantly expand the number and diversity of species for which density can be estimated.


Micromachines ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1015
Author(s):  
Mitsuru Sentoku ◽  
Hiromichi Hashimoto ◽  
Kento Iida ◽  
Masaharu Endo ◽  
Kenji Yasuda

Agarose photothermal microfabrication technology is one of the micropatterning techniques that has the advantage of simple and flexible real-time fabrication even during the cultivation of cells. To examine the ability and limitation of the agarose microstructures, we investigated the collective epithelial cell migration behavior in two-dimensional agarose confined structures. Agarose microchannels from 10 to 211 micrometer width were fabricated with a spot heating of a focused 1480 nm wavelength infrared laser to the thin agarose layer coated on the cultivation dish after the cells occupied the reservoir. The collective cell migration velocity maintained constant regardless of their extension distance, whereas the width dependency of those velocities was maximized around 30 micrometer width and decreased both in the narrower and wider microchannels. The single-cell tracking revealed that the decrease of velocity in the narrower width was caused by the apparent increase of aspect ratio of cell shape (up to 8.9). In contrast, the decrease in the wider channels was mainly caused by the increase of the random walk-like behavior of component cells. The results confirmed the advantages of this method: (1) flexible fabrication without any pre-designing, (2) modification even during cultivation, and (3) the cells were confined in the agarose geometry.


2012 ◽  
Vol 69 (3) ◽  
pp. 565-572 ◽  
Author(s):  
Colin A. Simpfendorfer ◽  
Esben M. Olsen ◽  
Michelle R. Heupel ◽  
Even Moland

Tracking data have previously been used to define animal movement patterns through two-dimensional (2D) kernel utilization distributions and separate analysis of vertical locations. Here we describe the use of three-dimensional (3D) kernel utilization distributions to estimate the volumetric space use of individuals based on tracking data and to estimate the overlap in activity space between individuals. Data from European eels ( Anguilla anguilla ) from Norwegian coastal waters were used to compare the information conveyed by 2D and 3D activity space estimates and the utility of this approach for aquatic species. The use of 3D kernels produced detailed representations of space use in A. anguilla that permitted examination of depth use in a geographic context. Comparison of 2D and 3D home ranges showed that 2D analyses overestimated the amount of overlap between individuals by 13%–20%, because individuals sometimes occurred in the same location but used different depths. Hence, the 3D approach provided more comprehensive representations of animal movement in three dimensions while producing a metric that can be used for testing hypotheses relating to scientific descriptions of activity space, habitat use, and movement parameters.


2017 ◽  
Author(s):  
Maria Kotini ◽  
Elias H. Barriga ◽  
Jonathan Leslie ◽  
Marc Gentzel ◽  
Alexandra Schambony ◽  
...  

AbstractConnexins are the primary components of gap junctions, providing direct links between cells in many physiological processes, including cell migration and cancer metastasis. Exactly how cell migration is controlled by gap junctions remains a mystery. To shed light on this, we investigated the role of Connexin43 in collective cell migration during embryo development using the neural crest, an embryonic cell population whose migratory behavior has been likened to cancer invasion. We discovered that Connexin43 is required for contact inhibition of locomotion by directly regulating the transcription of N-cadherin. For this function, the Connexin43 carboxy tail interacts with Basic Transcription Factor 3, which mediates its translocation to the nucleus. Together, they bind to the n-cad promotor regulating n-cad transcription. Thus, we uncover an unexpected, gap junction-independent role for Connexin43 in collective migration that illustrates the possibility that connexins, in general, may be important for a wide variety of cellular processes that we are only beginning to understand.HighlightsCx43 regulates collective directional migration of neural crest cellsCx43 carboxy tail controls cell polarity via n-cad regulationCx43 carboxy tail localises at the nucleus and that depends on BTF3BTF3 and Cx43 carboxy tail directly interact to bind and regulate n-cad promoter activity


2021 ◽  
Author(s):  
Mark Skamrahl ◽  
Hongtao Pang ◽  
Maximilian Ferle ◽  
Jannis Gottwald ◽  
Angela Rübeling ◽  
...  

AbstractTight junctions are pivotal components of epithelial tissues connecting neighboring cells to provide protective barriers. However, explicit knowledge of their role during other crucial biological processes, such as collective cell migration, remains sparse. Here, the importance of the tight junction proteins ZO1 and ZO2 for epithelial migration is investigated employing video microscopy in conjunction with velocimetry, segmentation, cell tracking, and atomic force microscopy/spectroscopy. The results indicate that ZO proteins are necessary for fast and coherent migration. In particular, ZO1 and 2 loss induces actomyosin remodeling away from the central cortex towards the periphery of individual cells, resulting in altered viscoelastic properties. A tug-of-war emerges between two cell populations with distinct morphological and mechanical properties: 1) smaller and highly contractile cells with an outwards bulged apical membrane, and 2) larger, flattened cells, which, due to tensile stress, display a higher proliferation rate. In response, the cell density increases, leading to crowding- induced jamming and more small cells over time. These smaller cells are particularly immobile and therefore drive jamming. Knockout of only ZO1 induces a similar but less pronounced behavior. This study shows that ZO proteins are necessary for efficient collective cell migration by maintaining tissue fluidity and controlling proliferation.


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