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 Self-organized cell migration across scales – from single cell movement to tissue formation

Development ◽  
2021 ◽  
Vol 148 (7) ◽  
pp. dev191767
Author(s):  
Jessica Stock ◽  
Andrea Pauli
Keyword(s):  
Cell Migration ◽  
Multiple Scales ◽  
Single Cells ◽  
Cell Movement ◽  
Biological Response ◽  
Collective Cell Migration ◽  
Theoretical Concepts ◽  
Self Organizing

ABSTRACTSelf-organization is a key feature of many biological and developmental processes, including cell migration. Although cell migration has traditionally been viewed as a biological response to extrinsic signals, advances within the past two decades have highlighted the importance of intrinsic self-organizing properties to direct cell migration on multiple scales. In this Review, we will explore self-organizing mechanisms that lay the foundation for both single and collective cell migration. Based on in vitro and in vivo examples, we will discuss theoretical concepts that underlie the persistent migration of single cells in the absence of directional guidance cues, and the formation of an autonomous cell collective that drives coordinated migration. Finally, we highlight the general implications of self-organizing principles guiding cell migration for biological and medical research.

scholarly journals Non-junctional Cadherin3 regulates cell migration and contact inhibition of locomotion via domain-dependent opposing regulations of Rac1

2019 ◽  
Author(s):  
Takehiko Ichikawa ◽  
Carsten Stuckenholz ◽  
Lance A. Davidson
Keyword(s):  
Cell Migration ◽  
Contact Inhibition ◽  
Cell Contact ◽  
Collective Cell Migration ◽  
Cell Contacts ◽  
Rac1 Activity ◽  
Classical Cadherins ◽  
The Stability ◽  
Cell Cell

AbstractClassical cadherins are well-known primary adhesion molecules responsible for physically connecting neighboring cells and signaling the cell-cell contact. Recent studies have suggested novel signaling roles for “non-junctional” cadherins (Niessen and Gottardi, 2008; Padmanabhan et al., 2017); however, the function of cadherin signaling independent of cell-cell contacts remains unknown. In this study, we used mesendoderm cells and tissues from gastrula stage Xenopus laevis embryos to demonstrate that extracellular and cytoplasmic cadherin domains regulate Rac1 in opposing directions in the absence of cell-cell contacts. Furthermore, we found that non-junctional cadherins regulate contact inhibition of locomotion (CIL) during gastrulation through alterations in the stability of the cytoskeleton. Live FRET imaging of Rac1 activity illustrated how non-junction cadherin3 (formerly C-cadherin) spatio-temporally regulates CIL. Our study provides novel insights into adhesion-independent signaling by cadherin3 and its role in regulating single and collective cell migration in vivo.

scholarly journals A least microenvironmental uncertainty principle (LEUP) as a generative model of collective cell migration mechanisms

2018 ◽  
Author(s):  
Arnab Barua ◽  
Josue M. Nava-Sedeño ◽  
Haralampos Hatzikirou
Keyword(s):  
Cell Migration ◽  
Uncertainty Principle ◽  
Collective Behavior ◽  
Cell Movement ◽  
Generative Model ◽  
Collective Cell Migration ◽  
Proof Of Concept ◽  
Collective Migration ◽  
Vicsek Model ◽  
Special Case

AbstractCollective migration is commonly observed in groups of migrating cells, in the form of swarms or aggregates. Mechanistic models have proven very useful in understanding collective cell migration. Such models, either explicitly consider the forces involved in the interaction and movement of individuals or phenomenologically define rules which mimic the observed behavior of cells. However, mechanisms leading to collective migration are varied and specific to the type of cells involved. Additionally, the precise and complete dynamics of many important chemomechanical factors influencing cell movement, from signalling pathways to substrate sensing, are typically either too complex or largely unknown. The question is how to make quantitative/qualitative predictions of collective behavior without exact mechanistic knowledge. Here we propose the least microenvironmental uncertainty principle (LEUP) that serves as a generative model of collective migration without incorporation of full mechanistic details. Interestingly we show that the famous Vicsek model is a special case of LEUP. Finally, as a proof of concept, we apply the LEUP to quantitatively study ofthe collective behavior of spherical Serratia marcescens bacteria, where the underlying migration mechanisms remain elusive.

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.

scholarly journals In vivo confinement promotes collective migration of neural crest cells

2016 ◽  
Vol 213 (5) ◽  
pp. 543-555 ◽  
Author(s):  
András Szabó ◽  
Manuela Melchionda ◽  
Giancarlo Nastasi ◽  
Mae L. Woods ◽  
Salvatore Campo ◽  
...  
Keyword(s):  
Cell Migration ◽  
Neural Crest ◽  
Neural Crest Cells ◽  
Optimal Number ◽  
Collective Cell Migration ◽  
Collective Migration ◽  
Extracellular Matrix Molecule ◽  
Experimental Approaches

Collective cell migration is fundamental throughout development and in many diseases. Spatial confinement using micropatterns has been shown to promote collective cell migration in vitro, but its effect in vivo remains unclear. Combining computational and experimental approaches, we show that the in vivo collective migration of neural crest cells (NCCs) depends on such confinement. We demonstrate that confinement may be imposed by the spatiotemporal distribution of a nonpermissive substrate provided by versican, an extracellular matrix molecule previously proposed to have contrasting roles: barrier or promoter of NCC migration. We resolve the controversy by demonstrating that versican works as an inhibitor of NCC migration and also acts as a guiding cue by forming exclusionary boundaries. Our model predicts an optimal number of cells in a given confinement width to allow for directional migration. This optimum coincides with the width of neural crest migratory streams analyzed across different species, proposing an explanation for the highly conserved nature of NCC streams during development.

scholarly journals A least microenvironmental uncertainty principle (LEUP) as a generative model of collective cell migration mechanisms

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Arnab Barua ◽  
Josue M. Nava-Sedeño ◽  
Michael Meyer-Hermann ◽  
Haralampos Hatzikirou
Keyword(s):  
Cell Migration ◽  
Uncertainty Principle ◽  
Collective Behavior ◽  
Statistical Physics ◽  
Cell Movement ◽  
Generative Model ◽  
Collective Cell Migration ◽  
Collective Migration ◽  
Vicsek Model ◽  
Special Case

AbstractCollective migration is commonly observed in groups of migrating cells, in the form of swarms or aggregates. Mechanistic models have proven very useful in understanding collective cell migration. Such models, either explicitly consider the forces involved in the interaction and movement of individuals or phenomenologically define rules which mimic the observed behavior of cells. However, mechanisms leading to collective migration are varied and specific to the type of cells involved. Additionally, the precise and complete dynamics of many important chemomechanical factors influencing cell movement, from signalling pathways to substrate sensing, are typically either too complex or largely unknown. The question is how to make quantitative/qualitative predictions of collective behavior without exact mechanistic knowledge. Here we propose the least microenvironmental uncertainty principle (LEUP) that may serve as a generative model of collective migration without precise incorporation of full mechanistic details. Using statistical physics tools, we show that the famous Vicsek model is a special case of LEUP. Finally, to test the biological applicability of our theory, we apply LEUP to construct a model of the collective behavior of spherical Serratia marcescens bacteria, where the underlying migration mechanisms remain elusive.

scholarly journals Modeling and analysis of collective cell migration in an in vivo three-dimensional environment

2016 ◽  
Vol 113 (15) ◽  
pp. E2134-E2141 ◽  
Author(s):  
Danfeng Cai ◽  
Wei Dai ◽  
Mohit Prasad ◽  
Junjie Luo ◽  
Nir S. Gov ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cluster Size ◽  
Single Cells ◽  
Theoretical Modeling ◽  
Relative Advantage ◽  
Viscous Drag ◽  
Collective Cell Migration ◽  
Nurse Cells ◽  
Egg Chamber

A long-standing question in collective cell migration has been what might be the relative advantage of forming a cluster over migrating individually. Does an increase in the size of a collectively migrating group of cells enable them to sample the chemical gradient over a greater distance because the difference between front and rear of a cluster would be greater than for single cells? We combined theoretical modeling with experiments to study collective migration of the border cells in-between nurse cells in the Drosophila egg chamber. We discovered that cluster size is positively correlated with migration speed, up to a particular point above which speed plummets. This may be due to the effect of viscous drag from surrounding nurse cells together with confinement of all of the cells within a stiff extracellular matrix. The model predicts no relationship between cluster size and velocity for cells moving on a flat surface, in contrast to movement within a 3D environment. Our analyses also suggest that the overall chemoattractant profile in the egg chamber is likely to be exponential, with the highest concentration in the oocyte. These findings provide insights into collective chemotaxis by combining theoretical modeling with experimentation.

Traction Force Measurement During Collective Cell Migration Measured by Multichannel Micropillar Device

2013 ◽  
Author(s):  
Toshiro Ohashi ◽  
Akito Sugawara
Keyword(s):  
Cell Migration ◽  
Soft Lithography ◽  
Force Measurement ◽  
Single Cells ◽  
Cell Movement ◽  
Traction Force ◽  
Collective Cell Migration ◽  
Maximum Magnitude ◽  
Traction Forces ◽  
Moving Front

Cell migration is essential for a variety of biological and pathological processes such as wound healing, inflammation and tumor metastasis. However, the mechanical environment within a group of cells during collective migration has not been well characterized. In this study, a polydimethylsiloxane (PDMS) multichannel device was fabricated using standard photolithography and soft lithography techniques and was used to monitor cellular traction forces during migration. A migration rate of 5.7 μm/h was measured in microchannels and leading cells in the moving front of the migration generated traction forces with a maximum magnitude of 14 nN at their front side. Traction forces generated by cells behind the leading cells directed forces backward at both the front and rear sides. However, traction forces generated by cells behind the second row had forces in random directions and with smaller magnitudes compared to those on the front and the second row. It is assumed that cells on the front line generated large traction forces and migrated actively as single cells, pulling adjacent cells forward, whereas the cell movement after the third row was restricted by mechanical linkages between their neighboring cells.

scholarly journals Roles of leader and follower cells in collective cell migration

2021 ◽  
Vol 32 (14) ◽  
pp. 1267-1272
Author(s):  
Lei Qin ◽  
Dazhi Yang ◽  
Weihong Yi ◽  
Huiling Cao ◽  
Guozhi Xiao
Keyword(s):  
Cell Migration ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Cell Movement ◽  
Special Focus ◽  
Collective Cell Migration ◽  
Force Transmission ◽  
Collective Movement

Collective cell migration is a widely observed phenomenon during animal development, tissue repair, and cancer metastasis. Considering its broad involvement in biological processes, it is essential to understand the basics behind the collective movement. Based on the topology of migrating populations, tissue-scale kinetics, called the “leader–follower” model, has been proposed for persistent directional collective movement. Extensive in vivo and in vitro studies reveal the characteristics of leader cells, as well as the special mechanisms leader cells employ for maintaining their positions in collective migration. However, follower cells have attracted increasing attention recently due to their important contributions to collective movement. In this Perspective, the current understanding of the molecular mechanisms behind the “leader–follower” model is reviewed with a special focus on the force transmission and diverse roles of leaders and followers during collective cell movement.

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