scholarly journals Modelling collective cell motion: are on- and off-lattice models equivalent?

2020 ◽  
Vol 375 (1807) ◽  
pp. 20190378 ◽  
Author(s):  
Josué Manik Nava-Sedeño ◽  
Anja Voß-Böhme ◽  
Haralampos Hatzikirou ◽  
Andreas Deutsch ◽  
Fernando Peruani
Keyword(s):  
Wound Repair ◽  
Collective Motion ◽  
Scale Effects ◽  
Lattice Models ◽  
Population Level ◽  
Collective Migration ◽  
Fruiting Body Formation ◽  
Bacterial Patterns ◽  
Dynamical Description ◽  
Cell Motion

Biological processes, such as embryonic development, wound repair and cancer invasion, or bacterial swarming and fruiting body formation, involve collective motion of cells as a coordinated group. Collective cell motion of eukaryotic cells often includes interactions that result in polar alignment of cell velocities, while bacterial patterns typically show features of apolar velocity alignment. For analysing the population-scale effects of these different alignment mechanisms, various on- and off-lattice agent-based models have been introduced. However, discriminating model-specific artefacts from general features of collective cell motion is challenging. In this work, we focus on equivalence criteria at the population level to compare on- and off-lattice models. In particular, we define prototypic off- and on-lattice models of polar and apolar alignment, and show how to obtain an on-lattice from an off-lattice model of velocity alignment. By characterizing the behaviour and dynamical description of collective migration models at the macroscopic level, we suggest the type of phase transitions and possible patterns in the approximative macroscopic partial differential equation descriptions as informative equivalence criteria between on- and off-lattice models. This article is part of the theme issue ‘Multi-scale analysis and modelling of collective migration in biological systems’.

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 Chemotactic Responses of Jurkat Cells in Microfluidic Flow-Free Gradient Chambers

Micromachines ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 384 ◽  
Author(s):  
Utku M. Sonmez ◽  
Adam Wood ◽  
Kyle Justus ◽  
Weijian Jiang ◽  
Fatima Syed-Picard ◽  
...  
Keyword(s):  
Immune Response ◽  
Cancer Progression ◽  
Soft Lithography ◽  
Cell Movement ◽  
Population Level ◽  
Jurkat Cells ◽  
Dependent Manner ◽  
Diverse Range ◽  
Microfluidic Flow ◽  
Cell Motion

Gradients of soluble molecules coordinate cellular communication in a diverse range of multicellular systems. Chemokine-driven chemotaxis is a key orchestrator of cell movement during organ development, immune response and cancer progression. Chemotaxis assays capable of examining cell responses to different chemokines in the context of various extracellular matrices will be crucial to characterize directed cell motion in conditions which mimic whole tissue conditions. Here, a microfluidic device which can generate different chemokine patterns in flow-free gradient chambers while controlling surface extracellular matrix (ECM) to study chemotaxis either at the population level or at the single cell level with high resolution imaging is presented. The device is produced by combining additive manufacturing (AM) and soft lithography. Generation of concentration gradients in the device were simulated and experimentally validated. Then, stable gradients were applied to modulate chemotaxis and chemokinetic response of Jurkat cells as a model for T lymphocyte motility. Live imaging of the gradient chambers allowed to track and quantify Jurkat cell migration patterns. Using this system, it has been found that the strength of the chemotactic response of Jurkat cells to CXCL12 gradient was reduced by increasing surface fibronectin in a dose-dependent manner. The chemotaxis of the Jurkat cells was also found to be governed not only by the CXCL12 gradient but also by the average CXCL12 concentration. Distinct migratory behaviors in response to chemokine gradients in different contexts may be physiologically relevant for shaping the host immune response and may serve to optimize the targeting and accumulation of immune cells to the inflammation site. Our approach demonstrates the feasibility of using a flow-free gradient chamber for evaluating cross-regulation of cell motility by multiple factors in different biologic processes.

Persistence of obligate-seeding species at the population scale: effects of fire intensity, fire patchiness and long fire-free intervals

2006 ◽  
Vol 15 (2) ◽  
pp. 261 ◽  
Author(s):  
Mark K. J. Ooi ◽  
Robert J. Whelan ◽  
Tony D. Auld
Keyword(s):  
Fire Regime ◽  
Scale Effects ◽  
Population Level ◽  
Fire Intensity ◽  
Adult Plant ◽  
Fire Response ◽  
Population Responses ◽  
Low Intensity ◽  
Plant Persistence ◽  
Fire Patchiness

Understanding how a species persists under a particular fire regime requires knowledge of the response to fire of individual plants. However, categorising the fire response of a species solely based on known responses of individual plants can be misleading when predicting a population response. In the present study, we sought to determine the fire responses of several Leucopogon species at the population level, including the threatened L. exolasius. We found that, whilst all species studied were obligate seeders, the population responses of species to fire were dependent upon fire intensity and patchiness. Results showed first that low intensity fires were significantly patchier than higher intensity fires. Second, the proportion of plants killed within a population decreased with increased fire patchiness. We also assessed how populations were structured and found that stands were multi-aged at most sites, and did not have a single-aged structure, which is often assumed for obligate seeders. Both spatial complexity within the fire regime leading to adult plant persistence, and inter-fire recruitment, contributed to the multi-aged structure. It is possible that these Leucopogon species are gap recruiters, and may tolerate fire rather than be specifically adapted to it. Inter-fire recruitment may enable L. exolasius populations to persist for a much longer fire-free period than many other species in the region.

scholarly journals Pressure drives rapid burst-like collective migration from 3D cancer aggregates

2021 ◽  
Author(s):  
Swetha Raghuraman ◽  
Ann-Sophie Schubert ◽  
Stephan Bröker ◽  
Alejandro Jurado ◽  
Annika Müller ◽  
...  
Keyword(s):  
Collective Motion ◽  
Migration And Invasion ◽  
Collective Migration ◽  
Collagen Concentration ◽  
Soft Matrix ◽  
Cell Velocity ◽  
Pulling Forces ◽  
Cervical Cancer Cells ◽  
New Evidence ◽  
Migration Of Cells

Collective migration of cells is a key behaviour observed during morphogenesis, wound healing and cancer cell invasion. Hence, understanding the different aspects of collective migration is at the core of further progress in describing and treating cancer and other pathological defects. The standard dogma in cell migration is that cells exert forces on the environment to move and cell-cell adhesion-based forces provide the coordination for collective migration. Here, we report a new collective migration mechanism that is independent of pulling forces on the extra-cellular matrix (ECM), as it is driven by the pressure difference generated inside model tumours. We observe a striking collective migration phenotype, where a rapid burst-like stream of HeLa cervical cancer cells emerges from the 3D aggregate embedded in matrices with low collagen concentration (0.5 mg ml−1). This invasion-like behaviour is recorded within 8 hours post embedding (hpe), and is characterised by high cell velocity and super-diffusive collective motion. We show that cellular swelling, triggered by the soft matrix, leads to a rise in intrinsic pressure, which eventually drives an invasion-like phenotype of HeLa cancer aggregates. These dynamic observations provide new evidence that pressure-driven effects need to be considered for a complete description of the mechanical forces involved in collective migration and invasion.

scholarly journals An analysis toolbox to explore mesenchymal migration heterogeneity reveals adaptive switching between distinct modes

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Hamdah Shafqat-Abbasi ◽  
Jacob M Kowalewski ◽  
Alexa Kiss ◽  
Xiaowei Gong ◽  
Pablo Hernandez-Varas ◽  
...  
Keyword(s):  
Scale Effects ◽  
Membrane Dynamics ◽  
Imaging Data ◽  
Actin Organization ◽  
Cell Matrix ◽  
Single Cell Imaging ◽  
High Adhesion ◽  
Behavioral Classification ◽  
Migratory Strategies ◽  
Cell Motion

Mesenchymal (lamellipodial) migration is heterogeneous, although whether this reflects progressive variability or discrete, 'switchable' migration modalities, remains unclear. We present an analytical toolbox, based on quantitative single-cell imaging data, to interrogate this heterogeneity. Integrating supervised behavioral classification with multivariate analyses of cell motion, membrane dynamics, cell-matrix adhesion status and F-actin organization, this toolbox here enables the detection and characterization of two quantitatively distinct mesenchymal migration modes, termed 'Continuous' and 'Discontinuous'. Quantitative mode comparisons reveal differences in cell motion, spatiotemporal coordination of membrane protrusion/retraction, and how cells within each mode reorganize with changed cell speed. These modes thus represent distinctive migratory strategies. Additional analyses illuminate the macromolecular- and cellular-scale effects of molecular targeting (fibronectin, talin, ROCK), including 'adaptive switching' between Continuous (favored at high adhesion/full contraction) and Discontinuous (low adhesion/inhibited contraction) modes. Overall, this analytical toolbox now facilitates the exploration of both spontaneous and adaptive heterogeneity in mesenchymal migration.

scholarly journals Cell growth rate dictates the onset of glass to fluid-like transition and long time super-diffusion in an evolving cell colony

2017 ◽  
Author(s):  
Abdul N Malmi-Kakkada ◽  
Xin Li ◽  
Himadri S. Samanta ◽  
Sumit Sinha ◽  
D. Thirumalai
Keyword(s):  
Growth Rate ◽  
Cell Growth ◽  
Tumor Invasion ◽  
Collective Motion ◽  
Mean Square Displacement ◽  
Tumor Evolution ◽  
Theoretic Approach ◽  
Cell Growth Rate ◽  
Collective Migration ◽  
Three Dimensional Model

Collective migration dominates many phenomena, from cell movement in living systems to abiotic self-propelling particles. Focusing on the early stages of tumor evolution, we enunciate the principles involved in cell dynamics and highlight their implications in understanding similar behavior in seemingly unrelated soft glassy materials and possibly chemokine-induced migration of CD8+T cells. We performed simulations of tumor invasion using a minimal three dimensional model, accounting for cell elasticity and adhesive cell-cell interactions as well as cell birth and death to establish that cell growth rate-dependent tumor expansion results in the emergence of distinct topological niches. Cells at the periphery move with higher velocity perpendicular to the tumor boundary, while motion of interior cells is slower and isotropic. The mean square displacement, Δ(t), of cells exhibits glassy behavior at times comparable to the cell cycle time, while exhibiting super-diffusive behavior, Δ(t) ≈tα(α> 1), at longer times. We derive the value ofα≈ 1.33 using a field theoretic approach based on stochastic quantization. In the process we establish the universality of super-diffusion in a class of seemingly unrelated non-equilibrium systems. Super diffusion at long times arises only if there is an imbalance between cell birth and death rates. Our findings for the collective migration, which also suggests that tumor evolution occurs in a polarized manner, are in quantitative agreement within vitroexperiments. Although set in the context of tumor invasion the findings should also hold in describing collective motion in growing cells and in active systems where creation and annihilation of particles play a role.

scholarly journals Bridging the gap between single-cell migration and collective dynamics

2019 ◽  
Author(s):  
Florian Thüroff ◽  
Andriy Goychuk ◽  
Matthias Reiter ◽  
Erwin Frey
Keyword(s):  
Cell Migration ◽  
Collective Motion ◽  
Single Cells ◽  
Cellular Migration ◽  
Coarse Grained ◽  
Collective Migration ◽  
Modeling Framework ◽  
Cell Functions ◽  
Cell Shapes ◽  
The Impact

AbstractA wealth of experimental data relating to the emergence of collective cell migration as one proceeds from the behavioral dynamics of small cohorts of cells to the coordinated migratory response of cells in extended tissues is now available. Integrating these findings into a mechanistic picture of cell migration that is applicable across such a broad range of system sizes constitutes a crucial step towards a better understanding of the basic factors that determine the emergence of collective cell motion. Here we present a cellular-automaton-based modeling framework, which focuses on the integration of high-level cell functions and their concerted effect on cellular migration patterns. In particular, we adopt a top-down approach to incorporate a coarse-grained description of cell polarity and its response to mechanical cues, and address the impact of cell adhesion on collective migration in cell groups. We demonstrate that the model faithfully reproduces typical cell shapes and movements down to the level of single cells, yet is computationally efficient enough to allow for the simulation of (currently) up to 𝒪(104) cells. To develop a mechanistic picture that illuminates the relationship between cell functions and collective migration, we present a detailed study of small groups of cells in confined circular geometries, and discuss the emerging patterns of collective motion in terms of specific cellular properties. Finally, we apply our computational model at the level of extended tissues, and investigate stress and velocity distributions, as well as front morphologies, in expanding cellular sheets.

scholarly journals A unifying framework for quantifying the nature of animal interactions

2014 ◽  
Vol 11 (96) ◽  
pp. 20140333 ◽  
Author(s):  
Jonathan R. Potts ◽  
Karl Mokross ◽  
Mark A. Lewis
Keyword(s):  
Spatial Patterns ◽  
Resource Selection ◽  
Collective Motion ◽  
Hand Movement ◽  
Population Level ◽  
Animal Behaviour ◽  
Motion Models ◽  
Special Cases ◽  
Selection Framework ◽  
Step Selection

Collective phenomena, whereby agent–agent interactions determine spatial patterns, are ubiquitous in the animal kingdom. On the other hand, movement and space use are also greatly influenced by the interactions between animals and their environment. Despite both types of interaction fundamentally influencing animal behaviour, there has hitherto been no unifying framework for the models proposed in both areas. Here, we construct a general method for inferring population-level spatial patterns from underlying individual movement and interaction processes, a key ingredient in building a statistical mechanics for ecological systems. We show that resource selection functions, as well as several examples of collective motion models, arise as special cases of our framework, thus bringing together resource selection analysis and collective animal behaviour into a single theory. In particular, we focus on combining the various mechanistic models of territorial interactions in the literature with step selection functions, by incorporating interactions into the step selection framework and demonstrating how to derive territorial patterns from the resulting models. We demonstrate the efficacy of our model by application to a population of insectivore birds in the Amazon rainforest.

scholarly journals Cell density and actomyosin contractility control the organization of migrating collectives within an epithelium

2016 ◽  
Vol 27 (22) ◽  
pp. 3459-3470 ◽  
Author(s):  
Andrew J. Loza ◽  
Sarita Koride ◽  
Gregory V. Schimizzi ◽  
Bo Li ◽  
Sean X. Sun ◽  
...  
Keyword(s):  
Wound Healing ◽  
Cell Density ◽  
Tumor Invasion ◽  
Collective Motion ◽  
Collective Migration ◽  
Migration Patterns ◽  
Genetic Manipulations ◽  
Actomyosin Contractility ◽  
Baseline State

The mechanisms underlying collective migration are important for understanding development, wound healing, and tumor invasion. Here we focus on cell density to determine its role in collective migration. Our findings show that increasing cell density, as might be seen in cancer, transforms groups from broad collectives to small, narrow streams. Conversely, diminishing cell density, as might occur at a wound front, leads to large, broad collectives with a distinct leader–follower structure. Simulations identify force-sensitive contractility as a mediator of how density affects collectives, and guided by this prediction, we find that the baseline state of contractility can enhance or reduce organization. Finally, we test predictions from these data in an in vivo epithelium by using genetic manipulations to drive collective motion between predicted migratory phases. This work demonstrates how commonly altered cellular properties can prime groups of cells to adopt migration patterns that may be harnessed in health or exploited in disease.

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