scholarly journals One-dimensional collective migration of a proliferating cell monolayer

Soft Matter ◽  
2016 ◽  
Vol 12 (8) ◽  
pp. 2381-2391 ◽  
Author(s):  
Pierre Recho ◽  
Jonas Ranft ◽  
Philippe Marcq
Keyword(s):  
Cell Proliferation ◽  
Cell Migration ◽  
Cell Monolayer ◽  
Spatial Dimension ◽  
Front Velocity ◽  
Collective Cell Migration ◽  
Collective Migration ◽  
Cell Sheets ◽  
One Dimensional ◽  
Proliferating Cell

Motivated by recent experiments on the expansion of highly cohesive cell sheets, our model of collective cell migration in one spatial dimension shows that constant front velocity results from the combined mechanical effects of bulk cell proliferation and front lamellipodial activity.

scholarly journals Integrin α5β1 nano-presentation regulates collective keratinocyte migration independent of substrate rigidity

2021 ◽  
Author(s):  
Jacopo Di Russo ◽  
Jennifer L. Young ◽  
Julian W. R. Wegner ◽  
Timmy Steins ◽  
Horst Kessler ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Cell Monolayer ◽  
Collective Cell Migration ◽  
Integrin Α5β1 ◽  
Migration Ability ◽  
Fibronectin Receptor ◽  
Substrate Rigidity ◽  
Scale Properties ◽  
Extracellular Matrix Receptors

AbstractNanometer-scale properties of the extracellular matrix influence many biological processes, including cell motility. While much information is available for single cell migration, to date, no knowledge exists on how the nanoscale presentation of extracellular matrix receptors influences collective cell migration. In wound healing, basal keratinocytes collectively migrate on a fibronectin-rich provisional basement membrane to re-epithelialize the injured skin. Among other receptors, the fibronectin receptor integrin α5β1 plays a pivotal role in this process. Using a highly specific integrin α5β1 peptidomimetic combined with nanopatterned hydrogels, we show that keratinocyte sheets regulate their migration ability at an optimal integrin α5β1 nanospacing. This efficiency relies on the effective propagation of stresses within the cell monolayer independent of substrate stiffness. For the first time, this work highlights the importance of extracellular matrix receptor nanoscale organization required for efficient tissue regeneration.

scholarly journals Heterogenous adhesion of follower cells affects tension profile and velocity of leader cells in primary keratocyte collective cell migration

2020 ◽  
Author(s):  
Baishali Mukherjee ◽  
Madhura Chakraborty ◽  
Arikta Biswas ◽  
Rajesh Kumble Nayak ◽  
Bidisha Sinha
Keyword(s):  
Cell Migration ◽  
Single Cell ◽  
Cell Interactions ◽  
Collective Cell Migration ◽  
Membrane Tension ◽  
High Cell ◽  
Cell Sheets ◽  
Membrane Fluctuations ◽  
High Tension ◽  
Cell To Cell Variability

AbstractSingle cell studies demonstrate membrane tension to be a central regulator of lamellipodia-driven motility bringing in front-coherence. During collective cell migration, however, tension mapping or existence of intracellular tension-gradients and the effect of cell-cell interactions have remained unexplored. In this study of membrane fluctuations and fluctuation-tension of migrating primary keratocyte cell-sheets, we first show that some leader cells are followed by followers which remain de-adhered from the substrate while being attached to other cells and thus appear to be “taking a ride”. A subtle yet significant enhanced long-timescale velocity in these leaders indicate increased directionality. Intriguingly, such leaders mostly have front-high tension gradients like single keratocytes, while followers and other leaders usually display front-low membrane tension gradients. The front-high tension gradient and higher membrane tension observed in these leaders, despite the high cell-to-cell variability in membrane tension demonstrate how leader-follower interactions and heterogenous adhesion profiles are key in collective cell migration.

scholarly journals Collective cell migration in development

2016 ◽  
Vol 212 (2) ◽  
pp. 143-155 ◽  
Author(s):  
Elena Scarpa ◽  
Roberto Mayor
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Collective Cell Migration ◽  
Germ Layer ◽  
Collective Migration ◽  
Developmental Models ◽  
Border Cell ◽  
Guidance Cues ◽  
Tracheal Branching

During embryonic development, tissues undergo major rearrangements that lead to germ layer positioning, patterning, and organ morphogenesis. Often these morphogenetic movements are accomplished by the coordinated and cooperative migration of the constituent cells, referred to as collective cell migration. The molecular and biomechanical mechanisms underlying collective migration of developing tissues have been investigated in a variety of models, including border cell migration, tracheal branching, blood vessel sprouting, and the migration of the lateral line primordium, neural crest cells, or head mesendoderm. Here we review recent advances in understanding collective migration in these developmental models, focusing on the interaction between cells and guidance cues presented by the microenvironment and on the role of cell–cell adhesion in mechanical and behavioral coupling of cells within the collective.

scholarly journals Hypoxia, Partial EMT and Collective Migration: Emerging Culprits in Metastasis

2020 ◽  
Author(s):  
Kritika Saxena ◽  
Mohit Kumar Jolly ◽  
Kuppusamy Balamurugan
Keyword(s):  
Drug Resistance ◽  
Cell Migration ◽  
Epithelial Mesenchymal Transition ◽  
Biological Process ◽  
Collective Cell Migration ◽  
Collective Migration ◽  
Mesenchymal Transition ◽  
Cancer Aggressiveness ◽  
Migration Of Cells ◽  
Successful Colonization

Epithelial-mesenchymal transition (EMT) is a cellular biological process involved in migration of primary cancer cells to secondary sites facilitating metastasis. Besides, EMT also confers properties such as stemness, drug resistance and immune evasion which can aid a successful colonization at the distant site. EMT is not a binary process; recent evidence suggests that cells in partial EMT or hybrid E/M phenotype(s) can have enhanced stemness and drug resistance as compared to those undergoing a complete EMT. Moreover, partial EMT enables collective migration of cells as clusters of circulating tumor cells or emboli, further endorsing that cells in hybrid E/M phenotypes may be the ‘fittest’ for metastasis. Here, we review mechanisms and implications of hybrid E/M phenotypes, including their reported association with hypoxia. Hypoxia-driven activation of HIF-1α can drive EMT. In addition, cyclic hypoxia, as compared to acute or chronic hypoxia, shows the highest levels of active HIF-1α and can augment cancer aggressiveness to a greater extent, including enriching for a partial EMT phenotype. We also discuss how metastasis is influenced by hypoxia, partial EMT and collective cell migration, and call for a better understanding of interconnections among these mechanisms. We discuss the known regulators of hypoxia, hybrid EMT and collective cell migration and highlight the gaps which needs to be filled for connecting these three axes which will increase our understanding of dynamics of metastasis and help control it more effectively.

scholarly journals Collective cell migration without proliferation: density determines cell velocity and wave velocity

2018 ◽  
Vol 5 (5) ◽  
pp. 172421 ◽  
Author(s):  
Sham Tlili ◽  
Estelle Gauquelin ◽  
Brigitte Li ◽  
Olivier Cardoso ◽  
Benoît Ladoux ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Density ◽  
Wave Velocity ◽  
Cell Monolayer ◽  
Leading Edge ◽  
Collective Cell Migration ◽  
Tumour Metastasis ◽  
Long Duration ◽  
Cell Velocity ◽  
Moving Front

Collective cell migration contributes to embryogenesis, wound healing and tumour metastasis. Cell monolayer migration experiments help in understanding what determines the movement of cells far from the leading edge. Inhibiting cell proliferation limits cell density increase and prevents jamming; we observe long-duration migration and quantify space–time characteristics of the velocity profile over large length scales and time scales. Velocity waves propagate backwards and their frequency depends only on cell density at the moving front. Both cell average velocity and wave velocity increase linearly with the cell effective radius regardless of the distance to the front. Inhibiting lamellipodia decreases cell velocity while waves either disappear or have a lower frequency. Our model combines conservation laws, monolayer mechanical properties and a phenomenological coupling between strain and polarity: advancing cells pull on their followers, which then become polarized. With reasonable values of parameters, this model agrees with several of our experimental observations. Together, our experiments and model disantangle the respective contributions of active velocity and of proliferation in monolayer migration, explain how cells maintain their polarity far from the moving front, and highlight the importance of strain–polarity coupling and density in long-range information propagation.

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 Aligned fibers direct collective cell migration to engineer closing and nonclosing wound gaps

2017 ◽  
Vol 28 (19) ◽  
pp. 2579-2588 ◽  
Author(s):  
Puja Sharma ◽  
Colin Ng ◽  
Aniket Jana ◽  
Abinash Padhi ◽  
Paige Szymanski ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Biology ◽  
Cancer Metastasis ◽  
Rubber Band ◽  
Cell Junctions ◽  
Collective Cell Migration ◽  
Cell Sheets ◽  
Cell Monolayers ◽  
Fiber Arrays

Cell emergence onto damaged or organized fibrous extracellular matrix (ECM) is a crucial precursor to collective cell migration in wound closure and cancer metastasis, respectively. However, there is a fundamental gap in our quantitative understanding of the role of local ECM size and arrangement in cell emergence–based migration and local gap closure. Here, using ECM-mimicking nanofibers bridging cell monolayers, we describe a method to recapitulate and quantitatively describe these in vivo behaviors over multispatial (single cell to cell sheets) and temporal (minutes to weeks) scales. On fiber arrays with large interfiber spacing, cells emerge (invade) either singularly by breaking cell–cell junctions analogous to release of a stretched rubber band (recoil), or in groups of few cells (chains), whereas on closely spaced fibers, multiple chains emerge collectively. Advancing cells on fibers form cell streams, which support suspended cell sheets (SCS) of various sizes and curvatures. SCS converge to form local gaps that close based on both the gap size and shape. We document that cell stream spacing of 375 µm and larger hinders SCS advancement, thus providing abilities to engineer closing and nonclosing gaps. Altogether we highlight the importance of studying cell-fiber interactions and matrix structural remodeling in fundamental and translational cell biology.

scholarly journals Expression of E-Cadherin in Epithelial Cancer Cells Increases Cell Motility and Directionality through the Localization of ZO-1 during Collective Cell Migration

2021 ◽  
Vol 8 (5) ◽  
pp. 65
Author(s):  
Song-Yi Park ◽  
Hwanseok Jang ◽  
Seon-Young Kim ◽  
Dasarang Kim ◽  
Yongdoo Park ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Motility ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Cell Contact ◽  
Collective Cell Migration ◽  
Collective Migration ◽  
Ags Cells ◽  
Mesenchymal Transition ◽  
E Cadherin

Collective cell migration of epithelial tumor cells is one of the important factors for elucidating cancer metastasis and developing novel drugs for cancer treatment. Especially, new roles of E-cadherin in cancer migration and metastasis, beyond the epithelial–mesenchymal transition, have recently been unveiled. Here, we quantitatively examined cell motility using micropatterned free edge migration model with E-cadherin re-expressing EC96 cells derived from adenocarcinoma gastric (AGS) cell line. EC96 cells showed increased migration features such as the expansion of cell islands and straightforward movement compared to AGS cells. The function of tight junction proteins known to E-cadherin expression were evaluated for cell migration by knockdown using sh-RNA. Cell migration and straight movement of EC96 cells were reduced by knockdown of ZO-1 and claudin-7, to a lesser degree. Analysis of the migratory activity of boundary cells and inner cells shows that EC96 cell migration was primarily conducted by boundary cells, similar to leader cells in collective migration. Immunofluorescence analysis showed that tight junctions (TJs) of EC96 cells might play important roles in intracellular communication among boundary cells. ZO-1 is localized to the base of protruding lamellipodia and cell contact sites at the rear of cells, indicating that ZO-1 might be important for the interaction between traction and tensile forces. Overall, dynamic regulation of E-cadherin expression and localization by interaction with ZO-1 protein is one of the targets for elucidating the mechanism of collective migration of cancer metastasis.

scholarly journals Collective cell migration without proliferation: density determines cell velocity and wave velocity

2017 ◽  
Author(s):  
Sham Tlili ◽  
Estelle Gauquelin ◽  
Brigitte Li ◽  
Olivier Cardoso ◽  
Benoît Ladoux ◽  
...  
Keyword(s):  
Cell Migration ◽  
Wave Velocity ◽  
Signal To Noise Ratio ◽  
Cell Monolayer ◽  
Temporal Analysis ◽  
Collective Cell Migration ◽  
Cell Radius ◽  
Cell Velocity ◽  
Spatio Temporal ◽  
Parameter Values

AbstractCollective cell migration contributes to morphogenesis, wound healing or tumor metastasis. Culturing epithelial monolayers on a substrate enables to quantify such tissue migration. By using narrow strips, we stabilise the front shape; by inhibiting cell division, we limit density increase and favor steady migration; by using long strips, we observe a confined cell monolayer migrating over days. A coherent collective movement propagates over millimeters; cells spread and density decreases from the monolayer bulk toward the front. Cell velocity (∼micrometer per minute) increases linearly with cell radius, and does not depend explicitly on the distance to the front. Over ten periods of backwards propagating velocity waves, with wavelength ∼millimeter, are detected with a signal-to-noise ratio enabling for quantitative spatio-temporal analysis. Their velocity (∼ten micrometers per minute) is ten times the cell velocity; it increases linearly with the cell radius. Their period (∼two hours) is spatially homogeneous, and increases with the front density. When we inhibit the formation of lamellipodia, cell velocity drops while waves either disappear, or have a smaller amplitude and slower period. Our phenomenological model assumes that both cell and wave velocities are related with the activity of lamellipodia, and that the local stretching in the monolayer bulk modulates traction stresses. We find that parameter values close to the instability limit where waves appear yield qualitative and quantitative predictions compatible with experiments, including the facts that: waves propagate backwards; wave velocity increases with cell radius; lamellipodia inhibition attenuates, slows down or even suppresses the waves. Together, our experiments and modelling evidence the importance of lamellipodia in collective cell migration and waves.

scholarly journals Confinement-induced transition between wave-like collective cell migration modes

2018 ◽  
Author(s):  
Vanni Petrolli ◽  
Magali Le Goff ◽  
Monika Tadrous ◽  
Kirsten Martens ◽  
Cédric Allier ◽  
...  
Keyword(s):  
Phase Transition ◽  
Cell Migration ◽  
Epithelial Cell ◽  
Functional Organization ◽  
Biological Tissues ◽  
Tissue Level ◽  
Collective Cell Migration ◽  
One Dimensional ◽  
Mechanical Signaling

The structural and functional organization of biological tissues relies on the intricate interplay between chemical and mechanical signaling. Whereas the role of constant and transient mechanical perturbations is generally accepted, several studies recently highlighted the existence of long-range mechanical excitations (i.e., waves) at the supracellular level. Here, we confine epithelial cell mono-layers to quasi-one dimensional geometries, to force the establishment of tissue-level waves of well-defined wavelength and period. Numerical simulations based on a self-propelled Voronoi model reproduce the observed waves and exhibit a phase transition between a global and a multi-nodal wave, controlled by the confinement size. We confirm experimentally the existence of such a phase transition, and show that wavelength and period are independent of the confinement length. Together, these results demonstrate the intrinsic origin of tissue oscillations, which could provide cells with a mechanism to accurately measure distances at the supracellular level.

Sign in / Sign up

Export Citation Format

Share Document