Who's really in charge: Diverse follower cell behaviors in collective cell migration

Campanale, Joseph P.; Montell, Denise J.

doi:10.1016/j.ceb.2023.102160

Cited by 14 publications

(4 citation statements)

References 50 publications

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“…Given that an autonomous leader appears to be unable to drag large cohorts of cells, our study raises the question of how leaders and followers communicate, if at all, to organize in the specific asymmetric patterns that enable collective cell migration. Candidate mechanisms include patterns in cell differentiation, paracrine signalling, or intercellular communication across cell junctions [65][66][67][68][69][70] . In contexts in which collective cell migration is not properly controlled, such as cancer invasion, mechanical asymmetries could be established stochastically, as observed in some of our experiments in which a few groups spontaneously developed a mechanical asymmetry and performed directed migration even in the absence of photoactivation (Fig.…”

Section: Discussionmentioning

confidence: 99%

Optogenetic generation of leader cells reveals a force-velocity relation for collective cell migration

Rossetti,

Grosser,

Abenza

et al. 2024

Preprint

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The front of migratory cellular clusters during development, wound healing and cancer invasion is typically populated with highly protrusive cells that are called leader cells. Leader cells are thought to physically pull and direct their cohort of followers, but how leaders and followers are mechanically organized to migrate collectively remains controversial. One possibility is that the autonomous local action of a leader cell is sufficient to drive migration of the group. Yet another possibility is that a global mechanical organization is required for the group to move cohesively. Here we show that the effectiveness of leader-follower organization is proportional to the asymmetry of traction and tension within the cellular cluster. By combining hydrogel micropatterning and optogenetic activation of Rac1, we locally generate highly protrusive leaders at the edge of minimal cell groups. We find that the induced leader can robustly drag one follower but is generally unable to direct larger groups. By measuring traction forces and tension propagation in groups of increasing size, we establish a quantitative relationship between group velocity and the asymmetry of the traction and tension profiles. We propose a model of the motile cluster as an active polar fluid that explains this force-velocity relationship in terms of asymmetries in the distribution of active tractions. Our results challenge the notion of autonomous leader cells by showing that collective cell migration requires a global mechanical organization within the cluster.

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Section: Discussionmentioning

confidence: 99%

Optogenetic generation of leader cells reveals a force-velocity relation for collective cell migration

Rossetti,

Grosser,

Abenza

et al. 2024

Preprint

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“…Several studies have shown that the contri- bution of the follower cells to the migrating clusters goes beyond simply being dragged along passively. 2,13,30 During the migration of zebrafish polster cells, follower cells guide their migration by pulling the leader cells from behind through E-cadherin/a-catenin mechanotransduction. 31 Another work shows that followers push the leader cells during the migration of posterior lateral line primordium (PLLp) migrating within the zebrafish embryo.…”

Section: Papermentioning

confidence: 99%

“…11,12 Follower cells that migrate after the leaders can also contribute passively or actively to collective migration. 13 They can push, pull, or even compete with leaders for their positions. Leader cells play a significant role in cancer metastasis, where cells migrate from one organ to another distant organ.…”

Section: Introductionmentioning

confidence: 99%

Photoactivatable substrates show diverse phenotypes of leader cells in collective migration when moving along different extracellular matrix proteins

Abdellatef,

Bard,

Nakanishi

2024

Biomater. Sci.

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“…1–4 In epithelial morphogenesis, wound healing, and regeneration processes, cells typically migrate in cohesive sheets attached to the extracellular matrix (ECM). 5,6 Perturbations of cellular motion lead to severe developmental defects, compromised wound healing, or even tumor formation. 1,7,8 Collective migration is a function of cell shape, cell-cell connectivity, cell-substrate adhesion, and active traction forces.…”

Section: Introductionmentioning

confidence: 99%

Cell-substrate distance fluctuations of confluent cells enable fast and coherent collective migration

Jipp,

Wagner,

Egbringhoff

et al. 2024

Preprint

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Collective cell migration is an emergent phenomenon, with long-range cell-cell communication influenced by various factors, including transmission of forces, viscoelasticity of individual cells, substrate interactions, and mechanotransduction. We investigate how alterations in cell-substrate dynamics, cell-substrate adhesion, and traction forces impact in-plane fluidity and temporal-spatial correlation of confluent monolayers comprising wild-type MDCK II cells or ZO1/2-depleted MDCK II cells (dKD). The combined data indicates that confluent dKD monolayers exhibit decreased in-plane fluidity compared to WT cells along with increased substrate adhesion, reduced traction forces, a more compact shape, diminished cell-cell interactions, and reduced cell-substrate height fluctuations. Depletion of basal actin and myosin further supports the notion that short-range cell-substrate interactions, particularly fluctuations driven by the basal actomyosin, significantly influence the migration speed of the monolayer on a larger length scale. Importantly, this in-plane fluidity proves to be highly compliant, requiring only a small portion of dynamic cells to maintain migration speed.

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Who's really in charge: Diverse follower cell behaviors in collective cell migration

Cited by 14 publications

References 50 publications

Optogenetic generation of leader cells reveals a force-velocity relation for collective cell migration

Optogenetic generation of leader cells reveals a force-velocity relation for collective cell migration

Photoactivatable substrates show diverse phenotypes of leader cells in collective migration when moving along different extracellular matrix proteins

Cell-substrate distance fluctuations of confluent cells enable fast and coherent collective migration

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