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Cell clusters adopt a collective amoeboid mode of migration in confined nonadhesive environments.

ABSTRACT: Cell migration is essential to living organisms and deregulated in cancer. Single cell's migration ranges from traction-dependent mesenchymal motility to contractility-driven propulsive amoeboid locomotion, but collective cell migration has only been described as a focal adhesion-dependent and traction-dependent process. Here, we show that cancer cell clusters, from patients and cell lines, migrate without focal adhesions when confined into nonadhesive microfabricated channels. Clusters coordinate and behave like giant super cells, mobilizing their actomyosin contractility at the rear to power their migration. This polarized cortex does not sustain persistent retrograde flows, of cells or actin, like in the other modes of migration but rather harnesses fluctuating cell deformations, or jiggling. Theoretical physical modeling shows this is sufficient to create a gradient of friction forces and trigger directed cluster motion. This collective amoeboid mode of migration could foster metastatic spread by enabling cells to cross a wide spectrum of environments.

SUBMITTER: Pages DL

PROVIDER: S-EPMC9524834 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Cell clusters adopt a collective amoeboid mode of migration in confined nonadhesive environments.

Pagès Diane-Laure DL Dornier Emmanuel E de Seze Jean J Gontran Emilie E Maitra Ananyo A Maciejewski Aurore A Wang Li L Luan Rui R Cartry Jérôme J Canet-Jourdan Charlotte C Raingeaud Joël J Lemahieu Grégoire G Lebel Marceline M Ducreux Michel M Gelli Maximiliano M Scoazec Jean-Yves JY Coppey Mathieu M Voituriez Raphaël R Piel Matthieu M Jaulin Fanny F

Science advances 20220930 39

Cell migration is essential to living organisms and deregulated in cancer. Single cell's migration ranges from traction-dependent mesenchymal motility to contractility-driven propulsive amoeboid locomotion, but collective cell migration has only been described as a focal adhesion-dependent and traction-dependent process. Here, we show that cancer cell clusters, from patients and cell lines, migrate without focal adhesions when confined into nonadhesive microfabricated channels. Clusters coordina ...[more]

PMID: 36179021

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Project description:Recent in vitro and in vivo studies have highlighted the importance of the cell nucleus in governing migration through confined environments. Microfluidic devices that mimic the narrow interstitial spaces of tissues have emerged as important tools to study cellular dynamics during confined migration, including the consequences of nuclear deformation and nuclear envelope rupture. However, while image acquisition can be automated on motorized microscopes, the analysis of the corresponding time-lapse sequences for nuclear transit through the pores and events such as nuclear envelope rupture currently requires manual analysis. In addition to being highly time-consuming, such manual analysis is susceptible to person-to-person variability. Studies that compare large numbers of cell types and conditions therefore require automated image analysis to achieve sufficiently high throughput. Here, we present an automated image analysis program to register microfluidic constrictions and perform image segmentation to detect individual cell nuclei. The MATLAB program tracks nuclear migration over time and records constriction-transit events, transit times, transit success rates, and nuclear envelope rupture. Such automation reduces the time required to analyze migration experiments from weeks to hours, and removes the variability that arises from different human analysts. Comparison with manual analysis confirmed that both constriction transit and nuclear envelope rupture were detected correctly and reliably, and the automated analysis results closely matched a manual analysis gold standard. Applying the program to specific biological examples, we demonstrate its ability to detect differences in nuclear transit time between cells with different levels of the nuclear envelope proteins lamin A/C, which govern nuclear deformability, and to detect an increase in nuclear envelope rupture duration in cells in which CHMP7, a protein involved in nuclear envelope repair, had been depleted. The program thus presents a versatile tool for the study of confined migration and its effect on the cell nucleus.

Dataset Information

Cell clusters adopt a collective amoeboid mode of migration in confined nonadhesive environments.

Publications

Cell clusters adopt a collective amoeboid mode of migration in confined nonadhesive environments.

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