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Collective and individual migration following the epithelial-mesenchymal transition.

Wong IY, Javaid S, Wong EA, Perk S, Haber DA, Toner M, Irimia D - Nat Mater (2014)

Bottom Line: Individual cells with few neighbours dispersed with fast, straight trajectories, whereas cells that encountered many neighbours migrated collectively with epithelial biomarkers.We modelled these emergent dynamics using a physical analogy to phase transitions during binary-mixture solidification, and validated it using drug perturbations, which revealed that individually migrating cells exhibit diminished chemosensitivity.Our measurements also indicate a degree of phenotypic plasticity as cells interconvert between individual and collective migration.

View Article: PubMed Central - PubMed

Affiliation: 1] BioMEMS Resource Center, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA [2].

ABSTRACT
During cancer progression, malignant cells in the tumour invade surrounding tissues. This transformation of adherent cells to a motile phenotype has been associated with the epithelial-mesenchymal transition (EMT). Here, we show that EMT-activated cells migrate through micropillar arrays as a collectively advancing front that scatters individual cells. Individual cells with few neighbours dispersed with fast, straight trajectories, whereas cells that encountered many neighbours migrated collectively with epithelial biomarkers. We modelled these emergent dynamics using a physical analogy to phase transitions during binary-mixture solidification, and validated it using drug perturbations, which revealed that individually migrating cells exhibit diminished chemosensitivity. Our measurements also indicate a degree of phenotypic plasticity as cells interconvert between individual and collective migration. The study of multicellular behaviours with single-cell resolution should enable further quantitative insights into heterogeneous tumour invasion.

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Differences in migratory behaviour associated with collective or individual migration phenotypes were classified using a Gaussian mixture modelThe lifetime-averaged nearest neighbours of the migrating cells are compared to (A) the final Y position in the device, (B) averaged velocity, and (C) path straightness. Overall, at the completion of the experiment, individually migrating cells are observed to the front with collectively migrating cells at the rear. (D) Single cell tracking reveals that individually migrating cells scatter effectively due to increases in speed and straighter trajectories, relative to collectively migrating cells.
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Figure 2: Differences in migratory behaviour associated with collective or individual migration phenotypes were classified using a Gaussian mixture modelThe lifetime-averaged nearest neighbours of the migrating cells are compared to (A) the final Y position in the device, (B) averaged velocity, and (C) path straightness. Overall, at the completion of the experiment, individually migrating cells are observed to the front with collectively migrating cells at the rear. (D) Single cell tracking reveals that individually migrating cells scatter effectively due to increases in speed and straighter trajectories, relative to collectively migrating cells.

Mentions: To classify these distinct collective or individual migration behaviours, a systematic comparison of the purely epithelial population (MCF-10A), the induced EMT population (MCF-10A Snail) and purely mesenchymal population (MDA-MB-231) was performed (Fig. 2, S6-9). For each population, the statistical distributions of four quantitative metrics were considered: (A) final Y position in the direction of migration; (B) lifetime-averaged number of nearest neighbours N; (C) lifetime-averaged velocity and (D) path straightness (displacement/integrated distance).


Collective and individual migration following the epithelial-mesenchymal transition.

Wong IY, Javaid S, Wong EA, Perk S, Haber DA, Toner M, Irimia D - Nat Mater (2014)

Differences in migratory behaviour associated with collective or individual migration phenotypes were classified using a Gaussian mixture modelThe lifetime-averaged nearest neighbours of the migrating cells are compared to (A) the final Y position in the device, (B) averaged velocity, and (C) path straightness. Overall, at the completion of the experiment, individually migrating cells are observed to the front with collectively migrating cells at the rear. (D) Single cell tracking reveals that individually migrating cells scatter effectively due to increases in speed and straighter trajectories, relative to collectively migrating cells.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4209198&req=5

Figure 2: Differences in migratory behaviour associated with collective or individual migration phenotypes were classified using a Gaussian mixture modelThe lifetime-averaged nearest neighbours of the migrating cells are compared to (A) the final Y position in the device, (B) averaged velocity, and (C) path straightness. Overall, at the completion of the experiment, individually migrating cells are observed to the front with collectively migrating cells at the rear. (D) Single cell tracking reveals that individually migrating cells scatter effectively due to increases in speed and straighter trajectories, relative to collectively migrating cells.
Mentions: To classify these distinct collective or individual migration behaviours, a systematic comparison of the purely epithelial population (MCF-10A), the induced EMT population (MCF-10A Snail) and purely mesenchymal population (MDA-MB-231) was performed (Fig. 2, S6-9). For each population, the statistical distributions of four quantitative metrics were considered: (A) final Y position in the direction of migration; (B) lifetime-averaged number of nearest neighbours N; (C) lifetime-averaged velocity and (D) path straightness (displacement/integrated distance).

Bottom Line: Individual cells with few neighbours dispersed with fast, straight trajectories, whereas cells that encountered many neighbours migrated collectively with epithelial biomarkers.We modelled these emergent dynamics using a physical analogy to phase transitions during binary-mixture solidification, and validated it using drug perturbations, which revealed that individually migrating cells exhibit diminished chemosensitivity.Our measurements also indicate a degree of phenotypic plasticity as cells interconvert between individual and collective migration.

View Article: PubMed Central - PubMed

Affiliation: 1] BioMEMS Resource Center, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA [2].

ABSTRACT
During cancer progression, malignant cells in the tumour invade surrounding tissues. This transformation of adherent cells to a motile phenotype has been associated with the epithelial-mesenchymal transition (EMT). Here, we show that EMT-activated cells migrate through micropillar arrays as a collectively advancing front that scatters individual cells. Individual cells with few neighbours dispersed with fast, straight trajectories, whereas cells that encountered many neighbours migrated collectively with epithelial biomarkers. We modelled these emergent dynamics using a physical analogy to phase transitions during binary-mixture solidification, and validated it using drug perturbations, which revealed that individually migrating cells exhibit diminished chemosensitivity. Our measurements also indicate a degree of phenotypic plasticity as cells interconvert between individual and collective migration. The study of multicellular behaviours with single-cell resolution should enable further quantitative insights into heterogeneous tumour invasion.

Show MeSH
Related in: MedlinePlus