Energy barriers and cell migration in densely packed tissues

Bi, Dapeng; Lopez, Jorge H.; Schwarz, J. M.; Manning, M. Lisa

doi:10.1039/c3sm52893f

Cited by 201 publications

(261 citation statements)

References 37 publications

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“…such as elastic, solid-like behaviour on short timescales and fluid-like cell rearrangements at longer timescales [41][42][43][44][45][46][47][48]. Consistent with this description, confluent epithelial and endothelial sheets show spontaneous stress fluctuations that can propagate many cell lengths across cell monolayers [44,46].…”

Section: Cs-l15supporting

confidence: 57%

Sphingosine 1-phosphate receptor 1 regulates the directional migration of lymphatic endothelial cells in response to fluid shear stress

Surya

Michalaki

Huang

et al. 2016

J. R. Soc. Interface.

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The endothelial cells that line blood and lymphatic vessels undergo complex, collective migration and rearrangement processes during embryonic development, and are known to be exquisitely responsive to fluid flow. At present, the molecular mechanisms by which endothelial cells sense fluid flow remain incompletely understood. Here, we report that both the G-protein-coupled receptor sphingosine 1-phosphate receptor 1 (S1PR1) and its ligand sphingosine 1-phosphate (S1P) are required for collective upstream migration of human lymphatic microvascular endothelial cells in an in vitro setting. These findings are consistent with a model in which signalling via S1P and S1PR1 are integral components in the response of lymphatic endothelial cells to the stimulus provided by fluid flow.

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Section: Cs-l15supporting

confidence: 57%

Sphingosine 1-phosphate receptor 1 regulates the directional migration of lymphatic endothelial cells in response to fluid shear stress

Surya

Michalaki

Huang

et al. 2016

J. R. Soc. Interface.

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“…There is no reason for the preferred area A 0 to be generically compatible with the preferred perimeter P 0 . This sets up a competition between the two terms in Eq (20), giving a natural scale that is determined by the relative ratio of GP Remarkably, one observes [49,59,86] a transition between a solid-like behaviour of the tissue, where cells do not exchange neighbours, and liquid-like behaviour, where neighbour exchanges do occur, at p 0 = 3.812, a value that corresponds to a regular pentagon. At present, the biological significance of this observation is not clear, but it appears to be a robust feature of many experimental systems [88].…”

Section: Activity Driven Fluidisation Phase Diagrammentioning

confidence: 99%

Active Vertex Model for Cell-Resolution Description of Epithelial Tissue Mechanics

Barton

Henkes

Weijer

et al. 2016

Preprint

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We introduce an Active Vertex Model (AVM) for cell-resolution studies of the mechanics of confluent epithelial tissues consisting of tens of thousands of cells, with a level of detail inaccessible to similar methods. The AVM combines the Vertex Model for confluent epithelial tissues with active matter dynamics. This introduces a natural description of the cell motion and accounts for motion patterns observed on multiple scales. Furthermore, cell contacts are generated dynamically from positions of cell centres. This not only enables efficient numerical implementation, but provides a natural description of the T1 transition events responsible for local tissue rearrangements. The AVM also includes cell alignment, cellspecific mechanical properties, cell growth, division and apoptosis. In addition, the AVM introduces a flexible, dynamically changing boundary of the epithelial sheet allowing for studies of phenomena such as the fingering instability or wound healing. We illustrate these capabilities with a number of case studies. Author summaryWe present a detailed analysis of the Active Vertex Model to study the mechanics of confluent epithelial tissues and cell monolayers. The model combines the commonly used Vertex Model for describing epithelial tissue mechanics with the active matter dynamics extensively studied in soft matter physics. We utlise an exact mathematical mapping that enables a very efficient numerical implementation using standard methods for simulating particle-based models. System sizes accessible to this model allow us to probe the dynamical motion patterns that occur in tissues over a range of length-and time-scales previously inaccessible to available simulation tools. Our model also includes a number of essential features required to properly describe actual biological systems such as cell growth, cell division and aptotsis, as well as the dynamic boundary of the epithelial sheet. This allows us to study phenomena such as the finger-like protrusions in cell monolayers and processes related to wound healing. The model is implemented into the SAMoS PLOS Computational Biology | https://doi

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“…However, cells are self-propelled and even in the absence of external forces, cells in confluent tissues regularly intercalate, or exchange neighbors [26,27]. In an isotropic confluent tissue monolayer where mitosis (cell division) or apoptosis (cell death) are rare, cell neighbor exchange must happen through intercalation processes known as T1 transitions [28,29], where an edge between two cells shrinks to a point and a new edge arises between two neighboring cells as illustrated in Fig. 1 (a).…”

Section: Figmentioning

confidence: 99%

A density-independent rigidity transition in biological tissues

Bi¹,

Lopez²,

Schwarz³

et al. 2015

Nature Phys

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709

1,033

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Cell migration is important in many biological processes, including embryonic development, cancer metastasis, and wound healing. In these tissues, a cell's motion is often strongly constrained by its neighbors, leading to glassy dynamics. While self-propelled particle models exhibit a density-driven glass transition, this does not explain liquid-to-solid transitions in confluent tissues, where there are no gaps between cells and therefore the density is constant. Here we demonstrate the existence of a new type of rigidity transition that occurs in the well-studied vertex model for confluent tissue monolayers at constant density. We find the onset of rigidity is governed by a model parameter that encodes single-cell properties such as cell-cell adhesion and cortical tension, providing an explanation for a liquid-to-solid transitions in confluent tissues and making testable predictions about how these transitions differ from those in particulate matter.Important biological processes such as embryogensis, tumorigenesis, and wound healing require cells to move collectively within a tissue. Recent experiments suggest that when cells are packed ever more densely, they start to exhibit collective motion [1][2][3] traditionally seen in non-living disordered systems such as colloids, granular matter or foams [4][5][6]. These collective behaviors exhibit growing timescales and lengthscales associated with rigidity transitions.Many of these effects are also seen in Self-Propelled Particle (SPP) models [7]. In SPP models, overdamped particles experience an active force that causes them to move at a constant speed, and particles change direction due to interactions with their neighbors or an external bath. To model cells with a cortical network of actomyosin and adhesive molecules on their surfaces, particles interact as repulsive disks or spheres, sometimes with an additional short-range attraction [8,9]. These models generically exhibit a glass transition at a critical packing density of particles, φ c , where φ c < 1 [1,8,10,11], and near the transition point they exhibit collective motion [8] that is very similar to that seen in experiments [12].An important open question is whether the density-driven glass transition in SPP models explains the glassy behavior observed in non-proliferating confluent biological tissues, where there are no gaps between cells and the packing fraction φ is fixed at precisely unity. For example, zebrafish embryonic explants are confluent three-dimensional tissues where the cells divide slowly and therefore the number of cells per unit volume remains nearly constant. Nevertheless, these tissues exhibit hallmarks of glassy dynamics such as caging behavior and viscoelasticity. Furthermore, ectoderm tissues have longer relaxation timescales than mesendoderm tissues, suggesting ectoderm tissues are closer to a glass transition, despite the fact that both tissue types have the same density [1]. This indicates that there should be an additional parameter controlling glass transitions in confluent ti...

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Energy barriers and cell migration in densely packed tissues

Cited by 201 publications

References 37 publications

Sphingosine 1-phosphate receptor 1 regulates the directional migration of lymphatic endothelial cells in response to fluid shear stress

Sphingosine 1-phosphate receptor 1 regulates the directional migration of lymphatic endothelial cells in response to fluid shear stress

Active Vertex Model for Cell-Resolution Description of Epithelial Tissue Mechanics

A density-independent rigidity transition in biological tissues

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