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.

Physiological ramifications of constrained collective cell migration

“…In vitro confinement of cells or cell clusters has been shown to induce specific, amoeboid‐like modes of migration independent of cell adhesion which may facilitate more efficient navigation within heterogeneous environments. [ 28,29 ]…”

“…In vitro confinement of cells or cell clusters has been shown to induce specific, amoeboid-like modes of migration independent of cell adhesion which may facilitate more efficient navigation within heterogeneous environments. [28,29] The direct relevance of adhesive micropatterns commonly used in vitro to the in vivo situation is somewhat less clear. However, the restriction in the migration space provided by the borders of these patterns can be thought of as representative of non-permissive cues confining migratory cells to defined regions.…”

Non-muscle myosin II and the plasticity of 3D cell migration

“…Importantly, this pool of cortical NMII activity at the rear of the cell also contributes to the movement of adherent mesenchymal cells using 3D lamellipodia-based migration (Lomakin et al, 2020) and we speculate it may be a universal feature of cells migrating through 3D matrices (Figure 2). Interestingly, when clusters of cells are confined within nonadhesive channels, they can switch their mode of migration from a traction force-based migration mechanism (Friedl et al, 2012) to an adhesion-independent amoeboid mode (Pages et al, 2022). This collective amoeboid movement requires RhoA activity and concentrated actomyosin contractility at plasma membranes of cells at the rear of the cluster where it helps to steer the cell cluster.…”

“…Interestingly, when clusters of cells are confined within non-adhesive channels, they can switch their mode of migration from a traction force-based migration mechanism ( Friedl et al, 2012 ) to an adhesion-independent amoeboid mode ( Pages et al, 2022 ). This collective amoeboid movement requires RhoA activity and concentrated actomyosin contractility at plasma membranes of cells at the rear of the cluster where it helps to steer the cell cluster.…”

The deformation of cancer cells through narrow micropores holds the potential to regulate genes that impact cancer malignancy

“…This platform facilitates real-time imaging of cancer cell migration. 30 In this study, we employed a commonly used method of subjecting breast cancer cells to passage through tiny pores to establish cell lines. This approach is widely utilized to discover novel biomarkers associated with cancer metastasis and drug resistance.…”