Plasticity and physical mechanisms of cell migration in confinement


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Ewa Paluch1
1University College London, London, UK

Abstract

Cell migration requires directional polarisation, usually achieved by the formation of a leading edge protrusion. Cells migrating in three-dimensional environments can form various protrusion types, including actin-filled lamellipodia and actomyosin contractility-driven blebs. The ability to switch between protrusion types has been proposed to facilitate motility in complex environments and to promote cancer dissemination. However, the minimal requirements and timescales of such plastic transitions are not known. Furthermore, while lamellipodia-driven migration has been extensively studied, the mechanisms underlying bleb-based migration are very poorly understood. We have been investigating these questions using Walker 256 carcinosarcoma cells, a rat tumour cell line that can form both blebs and lamellipodia during migration.

We showed that shifting the balance between actin protrusive activity and actomyosin contractility is sufficient to lead to immediate transitions between blebs and lamellipodia during cell migration. Such transitions could also be induced upon abrupt changes in the adhesiveness of the cell substrate.

We then asked how cell body translocation is achieved during bleb-based migration. We could show that this type of migration, common during tumour dissemination, does not require specific substrate adhesions as long as the cells are placed in a 3-dimensional environment. Using molecular and biophysical approaches combined with microfluidic engineering and physical modelling we showed that in Walker carcinosarcoma cells, force transmission during locomotion does not require trans-membrane coupling to the substrate. Instead, these cells appear to use a friction-based mechanism, translating intracellular cortical flows into forward movement of the cell body. Such a mechanism of locomotion, which does not rely on specific cell-substrate adhesions, may be advantageous for cells crossing multiple tissues, as it does not require the expression of tissue-specific receptors.