Size-dependent patterns of cell proliferation and migration in freely-expanding epithelia

Heinrich, Matthew A; Alert, Ricard; LaChance, Julienne; Zajdel, Tom J.; Košmrlj, Andrej; Cohen, Daniel

doi:10.7554/elife.58945

Cited by 49 publications

(100 citation statements)

References 66 publications

(99 reference statements)

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“…Thus, the model predicts that the average cellular area depends strongly on whether the tissue growth is before or after an avalanche. Furthermore, the model predicts the formation of tissue scale vortices during growth, in agreement with experiments (20).…”

Section: Resultssupporting

confidence: 82%

“…Interestingly, tissue scale vortex formation has been experimentally observed in growing epithelial monolayers (20). In addition, the radial profile of the vortex, formed during an avalanche, is consistent with the profile reported experimentally (20). For the cell trajectories without the onset of avalanches, see SI Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In both categories, cell motility and collective phenomena are a central theme. In the context of growth, a ubiquitous collective phenomenon, identified in vitro for both freely expanding and constrained growing cell tissues, is the formation of vortices by cell trajectories (18,20). Similar to our discovery of avalanches during growth, which is reported here, the vortices are a density driven collective phenomenon (18).…”

Section: Introductionmentioning

confidence: 99%

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Avalanches During Epithelial Tissue Growth; Uniform Growth and a Drosophila Eye Disc Model

Courcoubetis

Nuzhdin

et al. 2021

Preprint

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In the physicists’ perspective, epithelial tissues constitute an exotic type of active matter with non-linear properties reminiscent of amorphous materials. In the context of a circular proliferating epithelium, modeled by the quasistatic vertex model, we identify novel discrete tissue scale rearrangements, i.e. flow avalanches, which accomplish more compact tissue via cell slipping. After the onset of these avalanches, the epithelial area grows discontinuously. The avalanches are found to be stochastic, and their strength is determined by the density of cells in the tissue. Overall, avalanches regularize the spatial tension distribution along tissue. Furthermore, the avalanche distribution is found to obey a power law, with an exponent consistent with sheer induced avalanches in amorphous materials. To decipher the role of avalanches in organ development, we simulate epithelial growth of the Drosophila eye disc during the third instar using a computational model, which includes both signaling and mechanistic signalling. During the third instar, the morphogenetic furrow (MF), a ~10 cell wide wave of apical area constriction propagates through the epithelium, making it a system with interesting mechanical properties. These simulations are used to understand the details of the growth process, the effect of the MF on the growth dynamics on the tissue scale, and to make predictions. The avalanches are found to depend on the strength of the apical constriction of cells in the MF, with stronger apical constriction leading to less frequent and more pronounced avalanches. The results herein highlight the dependence of simulated tissue growth dynamics on relaxation timescales, motivate in vitro explorations and serve as a guide for future simulation implementations.

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Section: Resultssupporting

confidence: 82%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Avalanches During Epithelial Tissue Growth; Uniform Growth and a Drosophila Eye Disc Model

Courcoubetis

Nuzhdin

et al. 2021

Preprint

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“…1D,E). To reliably generate reproducible tissues and linear wounds, we use a silicone stencil templating method (12,35) to prepare confluent monolayers the evening before an experiment. We then assemble the electrobioreactor over these tissues prior to imaging.…”

Section: Resultsmentioning

confidence: 99%

Come together: bioelectric healing-on-a-chip

Zajdel

Shim

Cohen

2020

Preprint

Self Cite

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There is a growing interest in bioelectric wound treatment and electrotaxis, the process by which cells detect an electric field and orient their migration along its direction, has emerged as a potential cornerstone of the endogenous wound healing response. Despite recognition of the importance of electrotaxis in wound healing, no experimental system to date demonstrates that the actual closing of a wound can be accelerated solely by the electrotaxis response itself, and in vivo systems are too complex to resolve cell migration from other healing stages such as proliferation and inflammation. This uncertainty has led to a lack of standardization between stimulation methods, model systems, and electrode technology required for device development. In this paper, we present a ‘healing-on-chip’ approach that is a standardized, low-cost, model for investigating electrically accelerated wound healing. Our device provides the first convergent field geometry used in a stimulation device. We validate this device by using electrical stimulation to close a 1.5 mm gap between two large (30 mm2) primary skin keratinocyte layers to double the rate of healing over an unstimulated tissue. This proves that convergent electrotaxis is both possible and can accelerate healing, and offers a new ‘healing-on-a-chip’ platform to explore future bioelectric interfaces.

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“…A recent paper explores the relationship between initial tissue size and the dynamics of tissue growth [ 116 ].…”

Section: From Single To Collective Cell Behaviormentioning

confidence: 99%

Bridging from single to collective cell migration: A review of models and links to experiments

Buttenschön

Edelstein‐Keshet

2020

PLoS Comput Biol

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Mathematical and computational models can assist in gaining an understanding of cell behavior at many levels of organization. Here, we review models in the literature that focus on eukaryotic cell motility at 3 size scales: intracellular signaling that regulates cell shape and movement, single cell motility, and collective cell behavior from a few cells to tissues. We survey recent literature to summarize distinct computational methods (phase-field, polygonal, Cellular Potts, and spherical cells). We discuss models that bridge between levels of organization, and describe levels of detail, both biochemical and geometric, included in the models. We also highlight links between models and experiments. We find that models that span the 3 levels are still in the minority.

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Size-dependent patterns of cell proliferation and migration in freely-expanding epithelia

Cited by 49 publications

References 66 publications

Avalanches During Epithelial Tissue Growth; Uniform Growth and a Drosophila Eye Disc Model

Avalanches During Epithelial Tissue Growth; Uniform Growth and a Drosophila Eye Disc Model

Come together: bioelectric healing-on-a-chip

Bridging from single to collective cell migration: A review of models and links to experiments

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