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 Bridging the gap between single-cell migration and collective dynamics

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Florian Thüroff ◽  
Andriy Goychuk ◽  
Matthias Reiter ◽  
Erwin Frey
Keyword(s):  
Collective Motion ◽  
Single Cells ◽  
Cellular Migration ◽  
Coarse Grained ◽  
Modeling Framework ◽  
Actin Organization ◽  
Cell Functions ◽  
Typical Cell ◽  
Cell Shapes ◽  
The Impact

Motivated by the wealth of experimental data recently available, we present a cellular-automaton-based modeling framework focussing on high-level cell functions and their concerted effect on cellular migration patterns. Specifically, we formulate a coarse-grained description of cell polarity through self-regulated actin organization and its response to mechanical cues. Furthermore, we address the impact of cell adhesion on collective migration in cell cohorts. The model faithfully reproduces typical cell shapes and movements down to the level of single cells, yet allows for the efficient simulation of confluent tissues. In confined circular geometries, we find that specific properties of individual cells (polarizability; contractility) influence the emerging collective motion of small cell cohorts. Finally, we study the properties of expanding cellular monolayers (front morphology; stress and velocity distributions) at the level of extended tissues.

scholarly journals Cell migration guided by long-lived spatial memory

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Joseph d’Alessandro ◽  
Alex Barbier--Chebbah ◽  
Victor Cellerin ◽  
Olivier Benichou ◽  
René Marc Mège ◽  
...  
Keyword(s):  
Cell Migration ◽  
Spatial Memory ◽  
Large Scale ◽  
Single Cells ◽  
Environmental Perturbations ◽  
Motile Cells ◽  
Unicellular Organisms ◽  
Biochemical Signals ◽  
The Impact ◽  
Cell Trajectories

AbstractLiving cells actively migrate in their environment to perform key biological functions—from unicellular organisms looking for food to single cells such as fibroblasts, leukocytes or cancer cells that can shape, patrol or invade tissues. Cell migration results from complex intracellular processes that enable cell self-propulsion, and has been shown to also integrate various chemical or physical extracellular signals. While it is established that cells can modify their environment by depositing biochemical signals or mechanically remodelling the extracellular matrix, the impact of such self-induced environmental perturbations on cell trajectories at various scales remains unexplored. Here, we show that cells can retrieve their path: by confining motile cells on 1D and 2D micropatterned surfaces, we demonstrate that they leave long-lived physicochemical footprints along their way, which determine their future path. On this basis, we argue that cell trajectories belong to the general class of self-interacting random walks, and show that self-interactions can rule large scale exploration by inducing long-lived ageing, subdiffusion and anomalous first-passage statistics. Altogether, our joint experimental and theoretical approach points to a generic coupling between motile cells and their environment, which endows cells with a spatial memory of their path and can dramatically change their space exploration.

scholarly journals Cell migration driven by long-lived spatial memory

2021 ◽  
Author(s):  
Joseph d’Alessandro ◽  
Alex Barbier-Chebbah ◽  
Victor Cellerin ◽  
Olivier Bénichou ◽  
René-Marc Mège ◽  
...  
Keyword(s):  
Cell Migration ◽  
Spatial Memory ◽  
Large Scale ◽  
Single Cells ◽  
Environmental Perturbations ◽  
Motile Cells ◽  
Unicellular Organisms ◽  
Biochemical Signals ◽  
The Impact ◽  
Cell Trajectories

Many living cells actively migrate in their environment to perform key biological functions – from unicellular organisms looking for food to single cells such as fibroblasts, leukocytes or cancer cells that can shape, patrol or invade tissues. Cell migration results from complex intracellular processes that enable cell self-propulsion 1,2, and has been shown to also integrate various chemical or physical extracellular signals 3,4,5. While it is established that cells can modify their environment by depositing biochemical signals or mechanically remodeling the extracellular matrix, the impact of such self-induced environmental perturbations on cell trajectories at various scales remains unexplored. Here, we show that cells remember their path: by confining cells on 1D and 2D micropatterned surfaces, we demonstrate that motile cells leave long-lived physicochemical footprints along their way, which determine their future path. On this basis, we argue that cell trajectories belong to the general class of self-interacting random walks, and show that self-interactions can rule large scale exploration by inducing long-lived ageing, subdiffusion and anomalous first-passage statistics. Altogether, our joint experimental and theoretical approach points to a generic coupling between motile cells and their environment, which endows cells with a spatial memory of their path and can dramatically change their space exploration.

scholarly journals Alpha 1-antichymotrypsin contributes to stem cell characteristics and enhances tumorigenicity of Glioblastoma

2020 ◽  
Author(s):  
Montserrat Lara-Velazquez ◽  
Natanael Zarco ◽  
Anna Carrano ◽  
Jordan Phillipps ◽  
Emily S Norton ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Migration ◽  
Brain Tumor ◽  
Primary Cultures ◽  
Cellular Migration ◽  
Tumor Initiating Cells ◽  
The Impact

Abstract Background Glioblastomas (GBMs) are the most common primary brains tumors in adults with almost 100% recurrence rate. Patients with lateral ventricle proximal GBMs (LV-GBMs) exhibit worse survival compared to distal locations for reasons that remain unknown. One potential explanation is the proximity of these tumors to the cerebrospinal fluid (CSF) and its contained chemical cues that can regulate cellular migration and differentiation. We therefore investigated the role of CSF on GBM gene expression and the role of a CSF-induced gene, SERPINA3, in GBM malignancy in vitro and in vivo. Methods We utilized patient-derived CSF and primary cultures of GBM brain tumor initiating cells (BTICs). We determined the impact of SERPINA3 expression in glioma patients using TCGA database. SERPINA3 expression changes were evaluated at both the mRNA and protein levels. The effects of knockdown (KD) and overexpression (OE) of SERPINA3 on cell behavior were evaluated by transwell assay (for cell migration), and alamar blue and Ki67 (for viability and proliferation respectively). Stem cell characteristics on KD cells were evaluated by differentiation and colony formation experiments. Tumor growth was studied by intracranial and flank injections. Results GBM CSF induced a significant increase in BTIC migration accompanied by upregulation of the SERPINA3 gene. In patient samples and TCGA data we observed SERPINA3 to correlate directly with brain tumor grade and indirectly with GBM patient survival. Silencing of SERPINA3 induced a decrease in cell proliferation, migration, invasion, and stem cell characteristics, while SERPINA3 overexpression increased cell migration. In vivo, mice orthotopically-injected with SERPINA3 KD BTICs showed increased survival. Conclusions SERPINA3 plays a key role in GBM malignancy and its inhibition results in a better outcome using GBM preclinical models.

scholarly journals Pan-organ model integration of metabolic and regulatory processes in type 1 diabetes

2019 ◽  
Author(s):  
Marouen Ben Guebila ◽  
Ines Thiele
Keyword(s):  
Type 1 Diabetes ◽  
Systemic Disease ◽  
Coarse Grained ◽  
Whole Body ◽  
Correct Prediction ◽  
Long Term Effects ◽  
Modeling Framework ◽  
Human Pathology ◽  
The Impact

SummaryType 1 diabetes mellitus (T1D) is a systemic disease triggered by a local autoimmune inflammatory reaction in insulin-producing cells that disrupts the glucose-insulin-glucagon system and induces organ-wide, long-term effects on glycolytic and nonglycolytic processes. Mathematical modeling of the whole-body regulatory bihormonal system has helped to identify intervention points to ensure better control of T1D but was limited to a coarse-grained representation of metabolism. To extend the depiction of T1D, we developed a whole-body model using a novel integrative modeling framework that links organ-specific regulation and metabolism. The developed framework allowed the correct prediction of disrupted metabolic processes in T1D, highlighted pathophysiological processes common with neurodegenerative disorders, and suggested calcium channel blockers as potential adjuvants for diabetes control. Additionally, the model predicted the occurrence of insulin-dependent rewiring of interorgan crosstalk. Moreover, a simulation of a population of virtual patients allowed an assessment of the impact of inter and intraindividual variability on insulin treatment and the implications for clinical outcomes. In particular, GLUT4 was suggested as a potential pharmacogenomic regulator of intraindividual insulin efficacy. Taken together, the organ-resolved, dynamic model may pave the way for a better understanding of human pathology and model-based design of precise allopathic strategies.

scholarly journals Contact inhibition of locomotion probabilities drive solitary versus collective cell migration

2013 ◽  
Vol 10 (88) ◽  
pp. 20130717 ◽  
Author(s):  
Ravi A. Desai ◽  
Smitha B. Gopal ◽  
Sophia Chen ◽  
Christopher S. Chen
Keyword(s):  
Cell Migration ◽  
State Transition ◽  
Single Cells ◽  
Cell Movement ◽  
Contact Inhibition ◽  
Collective Cell Migration ◽  
Collective Migration ◽  
Agent Based ◽  
Solitary Cell

Contact inhibition of locomotion (CIL) is the process whereby cells collide, cease migrating in the direction of the collision, and repolarize their migration machinery away from the collision. Quantitative analysis of CIL has remained elusive because cell-to-cell collisions are infrequent in traditional cell culture. Moreover, whereas CIL predicts mutual cell repulsion and ‘scattering’ of cells, the same cells in vivo are observed to undergo CIL at some developmental times and collective cell migration at others. It remains unclear whether CIL is simply absent during collective cell migration, or if the two processes coexist and are perhaps even related. Here, we used micropatterned stripes of extracellular matrix to restrict cell migration to linear paths such that cells polarized in one of two directions and collisions between cells occurred frequently and consistently, permitting quantitative and unbiased analysis of CIL. Observing repolarization events in different contexts, including head-to-head collision, head-to-tail collision, collision with an inert barrier, or no collision, and describing polarization as a two-state transition indicated that CIL occurs probabilistically, and most strongly upon head-to-head collisions. In addition to strong CIL, we also observed ‘trains’ of cells moving collectively with high persistence that appeared to emerge from single cells. To reconcile these seemingly conflicting observations of CIL and collective cell migration, we constructed an agent-based model to simulate our experiments. Our model quantitatively predicted the emergence of collective migration, and demonstrated the sensitivity of such emergence to the probability of CIL. Thus CIL and collective migration can coexist, and in fact a shift in CIL probabilities may underlie transitions between solitary cell migration and collective cell migration. Taken together, our data demonstrate the emergence of persistently polarized, collective cell movement arising from CIL between colliding cells.

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 Potassium Channels Kv1.3 and Kir2.1 But Not Kv1.5 Contribute to BV2 Cell Line and Primary Microglial Migration

2021 ◽  
Vol 22 (4) ◽  
pp. 2081 ◽  
Author(s):  
Ruxandra Anton ◽  
Mihail Ghenghea ◽  
Violeta Ristoiu ◽  
Christophe Gattlen ◽  
Marc-Rene Suter ◽  
...  
Keyword(s):  
Cell Migration ◽  
Potassium Channels ◽  
Nerve Injury ◽  
Cellular Migration ◽  
Microglial Cells ◽  
Spared Nerve Injury ◽  
Cell Functions ◽  
Injury Model ◽  
Bv2 Cells ◽  
Underlying Mechanisms

(1) Background: As membrane channels contribute to different cell functions, understanding the underlying mechanisms becomes extremely important. A large number of neuronal channels have been investigated, however, less studied are the channels expressed in the glia population, particularly in microglia. In the present study, we focused on the function of the Kv1.3, Kv1.5 and Kir2.1 potassium channels expressed in both BV2 cells and primary microglia cultures, which may impact the cellular migration process. (2) Methods: Using an immunocytochemical approach, we were able to show the presence of the investigated channels in BV2 microglial cells, record their currents using a patch clamp and their role in cell migration using the scratch assay. The migration of the primary microglial cells in culture was assessed using cell culture inserts. (3) Results: By blocking each potassium channel, we showed that Kv1.3 and Kir2.1 but not Kv1.5 are essential for BV2 cell migration. Further, primary microglial cultures were obtained from a line of transgenic CX3CR1-eGFP mice that express fluorescent labeled microglia. The mice were subjected to a spared nerve injury model of pain and we found that microglia motility in an 8 µm insert was reduced 2 days after spared nerve injury (SNI) compared with sham conditions. Additional investigations showed a further impact on cell motility by specifically blocking Kv1.3 and Kir2.1 but not Kv1.5; (4) Conclusions: Our study highlights the importance of the Kv1.3 and Kir2.1 but not Kv1.5 potassium channels on microglia migration both in BV2 and primary cell cultures.

scholarly journals Quasi-periodic migration of single cells on short microlanes

2019 ◽  
Author(s):  
Fang Zhou ◽  
Sophia A. Schaffer ◽  
Christoph Schreiber ◽  
Felix J. Segerer ◽  
Andriy Goychuk ◽  
...  
Keyword(s):  
Cell Migration ◽  
Actin Polymerization ◽  
Molecular Mechanisms ◽  
Single Cells ◽  
Local Deformation ◽  
Physical Models ◽  
Cellular Potts Model ◽  
Periodic Movement ◽  
Cell Shapes ◽  
Cytoskeleton Dynamics

AbstractCell migration on microlanes represents a suitable and simple platform for the exploration of the molecular mechanisms underlying cell cytoskeleton dynamics. Here, we report on the quasi-periodic movement of cells confined in stripe-shaped microlanes. We observe persistent polarized cell shapes and directed pole-to-pole motion within the microlanes. Cells depolarize at one end of a given microlane, followed by delayed repolarization towards the opposite end. We analyze cell motility via the spatial velocity distribution, the velocity frequency spectrum and the reversal time as a measure for depolarization and spontaneous repolarization of cells at the microlane ends. The frequent encounters of a boundary in the stripe geometry provides a robust framework for quantitative investigations of the cytoskeleton protrusion and repolarization dynamics. In a first advance to rigorously test physical models of cell migration, we find that the statistics of the cell migration is recapitulated by a Cellular Potts model with a minimal description of cytoskeleton dynamics. Using LifeAct-GFP transfected cells and microlanes with differently shaped ends, we show that the local deformation of the leading cell edge in response to the tip geometry can locally either amplify or quench actin polymerization, while leaving the average reversal times unaffected.

scholarly journals Cell clusters adopt a collective amoeboid mode of migration in confined non-adhesive environments

2020 ◽  
Author(s):  
Diane-Laure Pagès ◽  
Emmanuel Dornier ◽  
Jean De Seze ◽  
Li Wang ◽  
Rui Luan ◽  
...  
Keyword(s):  
Cell Migration ◽  
Driving Forces ◽  
Single Cells ◽  
Focal Adhesions ◽  
Internal Flow ◽  
Collective Cell Migration ◽  
Collective Migration ◽  
Cell Clusters ◽  
Actin Cortex ◽  
Living Organisms

AbstractCell migration is essential to most living organisms. Single cell migration involves two distinct mechanisms, either a focal adhesion- and traction-dependent mesenchymal motility or an adhesion-independent but contractility-driven propulsive amoeboid locomotion. Cohesive migration of a group of cells, also called collective cell migration, has been only described as an adhesion- and traction-dependent mode of locomotion where the driving forces are mostly exerted at the front by leader cells. Here, by studying primary cancer specimens and cell lines from colorectal cancer, we demonstrate the existence of a second mode of collective migration which does not require adhesion to the surroundings and relies on a polarised supracellular contractility. Cell clusters confined into non-adhesive microchannels migrate in a rounded morphology, independently of the formation of focal adhesions or protruding leader cells, and lacking internal flow of cells, ruling-out classical traction-driven collective migration. Like single cells migrating in an amoeboid fashion, the clusters display a supracellular actin cortex with myosin II enriched at the rear. Using pharmacological inhibitors and optogenetics, we show that this polarised actomyosin activity powers migration and propels the clusters. This new mode of migration, that we named collective amoeboid, could be enabled by intrinsic or extrinsic neoplasic features to enable the metastatic spread of cancers.One Sentence SummaryClusters organise as polarised and contractile super-cells to migrate without adhesion.

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