Enhanced persistence and collective migration in cooperatively aligning cell clusters

Debets, Vincent E.; Janssen, Liesbeth M. C.; Storm, Cornelis

doi:10.1016/j.bpj.2021.02.014

Cited by 17 publications

(16 citation statements)

References 54 publications

(112 reference statements)

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“…Still, we here showed that these effects are not necessary to explain the observed density-dependent migration. This is also confirmed by recent modeling work by Debets et al (2021) , who showed a density-dependent speed and persistence increase for persistently migrating cell clusters of increasing size. In their work, cellular persistence is achieved by implementation of a persistent random walk combined with alignment within clusters that is achieved by explicit neighbor-induced cell polarity updates using a Vicsek model ( Debets et al, 2021 ).…”

Section: Discussionsupporting

confidence: 87%

“…This is also confirmed by recent modeling work by Debets et al (2021) , who showed a density-dependent speed and persistence increase for persistently migrating cell clusters of increasing size. In their work, cellular persistence is achieved by implementation of a persistent random walk combined with alignment within clusters that is achieved by explicit neighbor-induced cell polarity updates using a Vicsek model ( Debets et al, 2021 ). Our model is more mechanistic, because both cellular persistence and alignment emerge from the included single-cell pseudopod dynamics.…”

Section: Discussionsupporting

confidence: 87%

“…The Cellular Potts Model (CPM) ( Graner and Glazier, 1992 ; Glazier and Graner, 1993 ) is widely used for this purpose owing to its explicit incorporation of cell shape, and its flexibility to describe various biomechanical properties. For example, CPM has been used to model T cell migration behavior ( Beltman et al, 2007 ; Ariotti et al, 2012 ), collective cell migration ( Szabó et al, 2010 ; Kabla, 2012 ; Czirók et al, 2013 ; Szabó et al, 2016 ), chemotactic migration (using a hybrid CPM) ( Vroomans et al, 2012 ), traction forces by cells on 2D substrates ( Rens and Edelstein-Keshet, 2019 ), actin-inspired shape-driven cell migration ( Niculescu et al, 2015 ; Wortel et al, 2021b ), enhanced persistence in cooperatively aligning clusters ( Debets et al, 2021 ), and glassy dynamics of cells in confluent tissue ( Sadhukhan and Nandi, 2021 ) (see Szabó and Merks (2013) ; Sun and Zaman (2017) ; Buttenschön and Edelstein-Keshet (2020) for more elaborate reviews).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Density-Dependent Migration Characteristics of Cancer Cells Driven by Pseudopod Interaction

Burger

Water

Dévédec

et al. 2022

Front. Cell Dev. Biol.

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The ability of cancer cells to invade neighboring tissue from primary tumors is an important determinant of metastatic behavior. Quantification of cell migration characteristics such as migration speed and persistence helps to understand the requirements for such invasiveness. One factor that may influence invasion is how local tumor cell density shapes cell migration characteristics, which we here investigate with a combined experimental and computational modeling approach. First, we generated and analyzed time-lapse imaging data on two aggressive Triple-Negative Breast Cancer (TNBC) cell lines, HCC38 and Hs578T, during 2D migration assays at various cell densities. HCC38 cells exhibited a counter-intuitive increase in speed and persistence with increasing density, whereas Hs578T did not exhibit such an increase. Moreover, HCC38 cells exhibited strong cluster formation with active pseudopod-driven migration, especially at low densities, whereas Hs578T cells maintained a dispersed positioning. In order to obtain a mechanistic understanding of the density-dependent cell migration characteristics and cluster formation, we developed realistic spatial simulations using a Cellular Potts Model (CPM) with an explicit description of pseudopod dynamics. Model analysis demonstrated that pseudopods exerting a pulling force on the cell and interacting via increased adhesion at pseudopod tips could explain the experimentally observed increase in speed and persistence with increasing density in HCC38 cells. Thus, the density-dependent migratory behavior could be an emergent property of single-cell characteristics without the need for additional mechanisms. This implies that pseudopod dynamics and interaction may play a role in the aggressive nature of cancers through mediating dispersal.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Density-Dependent Migration Characteristics of Cancer Cells Driven by Pseudopod Interaction

Burger

Water

Dévédec

et al. 2022

Front. Cell Dev. Biol.

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“…5(D) shows the statistics of persistence times as a function of cluster size, indicating that the persistence time of the cluster increases as the cluster size gets larger until around N c = 5 where it plateaus. This is reminiscent of a recent work looking at the persistence time of Vicsek aligning Brownian particles [65]. In that paper, the persistence time of clusters increases linearly with the size of the cluster.…”

Section: Resultsmentioning

confidence: 62%

Collective chemotaxis in a Voronoi model for confluent clusters

Lawson-Keister

Manning

2021

Preprint

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Collective chemotaxis, where single cells cannot climb a biochemical signaling gradient but clusters of cells can, has been observed in different biological contexts, including confluent tissues where there are no gaps or overlaps between cells. Although particle-based models have been developed that predict important features of collective chemotaxis, the mechanisms in those models depend on particle overlaps, and so it remains unclear if they can explain behavior in confluent systems. Here, we develop an opensource code that couples a 2D Voronoi simulation for confluent cell mechanics to a dynamic chemical signal that can diffuse, advect, and/or degrade, and use the code to study potential mechanisms for collective chemotaxis in cellular monolayers. We first study the impact of advection on collective chemotaxis, and delineate a regime where advective terms are important. Next, we investigate two possible chemotactic mechanisms, contact inhibition of locomotion and heterotypic interfacial tension, and demonstrate that both can drive collective chemotaxis in certain parameter regimes. We further demonstrate that the scaling behavior of cluster motion is well-captured by simple analytic theories.1Statement of SignificanceThe ability of cell collectives to respond to biochemical signals, called collective chemotaxis, is crucial for many important processes including embryonic development and wound healing. We developed an opensource computational model that couples biochemical signaling gradients to confluent cell layers, where there are no gaps between cells. Our model demonstrates that two experimentally observed local cell behaviors – neighbor-induced changes to interfacial tension or a tendency of cells to repel one another after they come into contact – can drive collective chemotaxis. We also highlight a regime in which the motion of migrating cells can alter the gradient.

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“…Understanding the collective cell migration of these groups of cells is essential to the study of embryonic development, wound healing, and cancer metastasis [1–4]. Groups of cells can have different properties than single cells, including the ability to sense shallower chemical or mechanical gradients [5–13], the ability to amplify cues and develop guided migration over long distances reminiscent of the swarming behavior in insects [14, 15], and an increased efficacy of cancer metastasis [16]. These properties arise from intercellular interactions, including in particular the effect of direct cell-cell contact.…”

Section: Introductionmentioning

confidence: 99%

Picking winners in cell-cell collisions: wetting, speed, and contact

Zadeh

Camley

2022

Preprint

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Groups of eukaryotic cells can coordinate their crawling motion to follow cues more effectively, stay together, or invade new areas. This collective cell migration depends on cell-cell interactions, which are often studied by colliding pairs of cells together. Can the outcome of these collisions be predicted? Recent experiments on trains of colliding epithelial cells suggest that cells with a smaller contact angle to the surface or larger speeds are more likely to maintain their direction (“win”) upon collision. When should we expect shape or speed to correlate with the outcome of a collision? We build a model for two-cell collisions within the phase field approach, which treats cells as deformable objects. We can reproduce the observation that cells with high speed and small contact angles are more likely to win with two different assumptions for how cells interact: (1) velocity-aligning, in which we hypothesize that cells sense their own velocity and align to it over a finite timescale, and (2) front-front contact repolarization, where cells polarize away from cell-cell contact, akin to contact inhibition of locomotion. Surprisingly, though we simulate collisions between cells with widely varying properties, in each case, the probability of a cell winning is completely captured by a single summary variable: its relative speed (in the velocity-aligning model) or its relative contact angle (in the contact repolarization model). Both models are currently consistent with reported experimental results, but they can be distinguished by varying cell contact angle and speed through orthogonal perturbations.

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Enhanced persistence and collective migration in cooperatively aligning cell clusters

Cited by 17 publications

References 54 publications

Density-Dependent Migration Characteristics of Cancer Cells Driven by Pseudopod Interaction

Density-Dependent Migration Characteristics of Cancer Cells Driven by Pseudopod Interaction

Collective chemotaxis in a Voronoi model for confluent clusters

Picking winners in cell-cell collisions: wetting, speed, and contact

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