Unjamming and cell shape in the asthmatic airway epithelium

Park, Jin Ah; Kim, Jae‐Hun; Bi, Dapeng; Mitchel, Joseph F.; Qazvini, Nader Taheri; Tantisira, Kelan G.; Park, Chan Young; McGill, Maureen; Kim, Sae Hoon; Gweon, Bomi; Notbohm, Jacob; Steward, Robert L.; Burger, Stephanie; Randell, Scott H.; Kho, Alvin T.; Tambe, Dhananjay; Hardin, Corey; Shore, Stephanie A.; Israel, Elliot; Weitz, David A.; Tschumperlin, Daniel J.; Henske, Elizabeth P.; Weiss, Scott T.; Manning, M. Lisa; Butler, James P.; Drazen, Jeffrey M.; Fredberg, Jeffrey J.

doi:10.1038/nmat4357

Cited by 530 publications

(763 citation statements)

References 58 publications

(123 reference statements)

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“…The collective motion of a cell layer as it invades an empty region has been extensively studied experimentally (7-10) but the relation with the glassy features observed in confluent layers (34,35) was not explored. The externally driven motion of disordered and glassy systems typically involves intermittent behavior and avalanches (28).…”

Section: Discussionmentioning

confidence: 99%

Bursts of activity in collective cell migration

Chepizhko

Giampietro

Mastrapasqua

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Dense monolayers of living cells display intriguing relaxation dynamics, reminiscent of soft and glassy materials close to the jamming transition, and migrate collectively when space is available, as in wound healing or in cancer invasion. Here we show that collective cell migration occurs in bursts that are similar to those recorded in the propagation of cracks, fluid fronts in porous media, and ferromagnetic domain walls. In analogy with these systems, the distribution of activity bursts displays scaling laws that are universal in different cell types and for cells moving on different substrates. The main features of the invasion dynamics are quantitatively captured by a model of interacting active particles moving in a disordered landscape. Our results illustrate that collective motion of living cells is analogous to the corresponding dynamics in driven, but inanimate, systems.collective cell migration | avalanches | universality | vascular endothelial cadherin | collagen substrate C ollective cell movement depends on intracellular biological mechanisms as well as environmental cues due to the extracellular matrix (1-5), mainly composed of collagen which is organized in hierarchical structures, such as fibrils and fibers. The mechanical properties of collagen fibril networks are essential to offer little resistance and high sensitivity to small deformations, allowing easy local remodeling and strong strain stiffening needed to ensure cell and tissue integrity (6). Wound healing is a typical biological assay to study collective migration of cells under controlled conditions in vitro and is a prototypical experimental method to study active matter (7-10). Experiments performed on soluble collagen (11) or other gels (12), micropatterned (13, 14) and deformable substrates (1) show that cell migration is guided by the substrate structure and stiffness (5,15,16).It has been argued that collective migration properties arise from stresses transmitted between neighboring cells (1) giving rise to longranged stress waves in the monolayer (17,18). Hence the dynamics of an invading cell sheet is ruled by a combination of long-range internal stresses and interactions with the substrate, suggesting an analogy with driven elastic systems moving in a disordered medium such as cracks lines (19,20), imbibition fronts (21), or ferromagnetic domain walls (22). The scaling laws in these systems are usually associated with a depinning critical point that has been widely studied by simple models for interface dynamics. Thanks to a combination of numerical simulations (23, 24) and renormalization group theory (23,(25)(26)(27), we now have a detailed picture of the nonequilibrium phase transitions and universality classes in these systems. Here we substantiate the analogy between collective cell migration and depinning by revealing and characterizing widely distributed bursts of activity in the collective migration of different types of cells (human cancer cells and epithelial cells, mouse endothelial cells) over different substrates ...

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Section: Discussionmentioning

confidence: 99%

Bursts of activity in collective cell migration

Chepizhko

Giampietro

Mastrapasqua

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…This results in a so-called glassy solid that has been reasoned to correspond to any stable tissue with homeostatic epithelial cell packing . But if the energy barrier might somehow be overcome, say by enhanced cellular propulsive forces, or if the energy barrier itself might somehow be diminished -or even abolished altogether -as by the mechanisms described below, then the cell could escape its cage more readily; in a variety of such cellular collectives, the characteristic scales of time and length for such cellular rearrangements have been quantified Garcia et al, 2015;Nnetu et al, 2013;Park et al, 2015b). Such events would facilitate cellular rearrangements among neighbors, and ultimately the collective as a whole could therefore unjam and flow (Bi et al, 2015(Bi et al, , 2016Park et al, 2015b).…”

Section: Fluid-like Versus Solid-like Collective Phasesmentioning

confidence: 99%

“…But if the energy barrier might somehow be overcome, say by enhanced cellular propulsive forces, or if the energy barrier itself might somehow be diminished -or even abolished altogether -as by the mechanisms described below, then the cell could escape its cage more readily; in a variety of such cellular collectives, the characteristic scales of time and length for such cellular rearrangements have been quantified Garcia et al, 2015;Nnetu et al, 2013;Park et al, 2015b). Such events would facilitate cellular rearrangements among neighbors, and ultimately the collective as a whole could therefore unjam and flow (Bi et al, 2015(Bi et al, , 2016Park et al, 2015b). Such unjamming might be the case in the advancing of a confluent cell layer into unfilled space to heal a wound, embryonic development, morphogenesis or invasion of cancer cells into a healthy tissue Das et al, 2015;Fischer et al, 2015;Haeger et al, 2014;Serra-Picamal et al, 2012;Zheng et al, 2015).…”

Section: Fluid-like Versus Solid-like Collective Phasesmentioning

confidence: 99%

Collective migration and cell jamming in asthma, cancer and development

Park

Atia

Mitchel

et al. 2016

Journal of Cell Science

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132

159

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Collective cellular migration within the epithelial layer impacts upon development, wound healing and cancer invasion, but remains poorly understood. Prevailing conceptual frameworks tend to focus on the isolated role of each particular underlying factor -taken one at a time or at most a few at a time -and thus might not be tailored to describe a cellular collective that embodies a wide palette of physical and molecular interactions that are both strong and complex. To bridge this gap, we shift the spotlight to the emerging concept of cell jamming, which points to only a small set of parameters that govern when a cellular collective might jam and rigidify like a solid, or instead unjam and flow like a fluid. As gateways to cellular migration, the unjamming transition (UJT) and the epithelial-to-mesenchymal transition (EMT) share certain superficial similarities, but their congruence -or lack thereof -remains unclear. In this Commentary, we discuss aspects of cell jamming, its established role in human epithelial cell layers derived from the airways of nonasthmatic and asthmatic donors, and its speculative but emerging roles in development and cancer cell invasion.

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“…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]. In order to make the comparison between the AVM and the SPV model, we also adopt p 0 as a main parameter that controls the preferred cell shape.…”

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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Unjamming and cell shape in the asthmatic airway epithelium

Cited by 530 publications

References 58 publications

Bursts of activity in collective cell migration

Bursts of activity in collective cell migration

Collective migration and cell jamming in asthma, cancer and development

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

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