Deciphering collective amoeboid migration, a second mode of collective migration – collamoeboid

Deciphering collective amoeboid migration, a second mode of collective motion

The scope of this research program is to decrypt the fundamental mechanisms underlying a new mode of migration that we named “collective amoeboid”. While single cell migration is known to occur through two distinct mechanisms, based on traction (mesenchymal) or propulsion (amoeboid), collective migration has only been described as a traction-dependent mechanism mostly operated by leader cells.
Our unpublished results, obtained from primary tissue explants and cell lines, demonstrate that cell cohorts can also migrate in non-adhesive environments when they are confined. The clusters proceed without the formation of focal adhesion and rather rely on their actomyosin contractility to be propelled. We aim at deciphering the mechanisms underlying this new mode of cell migration by solving the following questions:

i) How is Front-back polarity set-up?
ii) How are forces generated and transmitted in the migrating cluster?
iii) Is there a leader/follower organization operating this mode of collective migration?
iv) Does the concept of plasticity, i.e. the alternance of traction and propulsion-driven motility, apply to collective migration?
v) What are the normal and pathological contexts in which collective amoeboid migration is enabled?

Our multidisciplinary consortium will combine modelling, microfluidics, optogenetics and microscopy-based approaches to resolve these open questions. Based on robust preliminary results we expect this research program to impact fundamental Science by reporting and characterizing a fourth mode of cell migration. The outcome of this proposal could also open avenues of biomedical research as collective amoeboid migration seems to be preferentially activated by cancer cell clusters in their metastatic spread.