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MECOLLACT
Mechanotransduction of cell collective behaviors through the actin cytoskeleton
FunderFrench National Research Agency (ANR)
Funder Contribution €593,570.00
DurationFrom 01 Mar 2021
Project codeANR-20-CE13-0016
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Description
Cells stop migrating and proliferating when they are densely packed (jamming). Upon wound healing or other mechanical treatments, cells resume migration and cell cycle progression (unjamming). Groups of cells are coordinated through actin-dependent mechanotransduction at cell-cell junctions. Our goal is to implicate novel molecules in this coordination. Since the RAC1-WAVE-Arp2/3 (RWA) pathway is involved in unjamming, we will study, using loss-of-function approaches and rescue with WT or mutant forms, several candidates that we identified by correlation with RWA in dependency maps. In MCF10A cell cultures and gastrulating zebrafish embryos, coordination of cell groups in collective migration will be analysed using physics tools and concepts (laser ablation, magnetic beads, active nematics). Using in vitro reconstitutions of cell-cell junctions, our candidate proteins will be directly implicated in the mechanotransduction of cytoskeletal forces or in its regulation.
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Cells stop migrating and proliferating when they are densely packed (jamming). Upon wound healing or other mechanical treatments, cells resume migration and cell cycle progression (unjamming). Groups of cells are coordinated through actin-dependent mechanotransduction at cell-cell junctions. Our goal is to implicate novel molecules in this coordination. Since the RAC1-WAVE-Arp2/3 (RWA) pathway is involved in unjamming, we will study, using loss-of-function approaches and rescue with WT or mutant forms, several candidates that we identified by correlation with RWA in dependency maps. In MCF10A cell cultures and gastrulating zebrafish embryos, coordination of cell groups in collective migration will be analysed using physics tools and concepts (laser ablation, magnetic beads, active nematics). Using in vitro reconstitutions of cell-cell junctions, our candidate proteins will be directly implicated in the mechanotransduction of cytoskeletal forces or in its regulation.
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