Venue : CGFB
Thesis defense in english
Team : Spatio-temporal and mechanical control of motile structures
Thèse dirigée par : Olivier Rossier
Deciphering the molecular links between actomyosin force, integrin regulation and ECM properties through an in vitro reconstitution
In cancer, 90% of deaths are due to the formation of metastases in which migration is deregulated. Among the motile structures affected are focal adhesions (FAs), which enable cells to grasp and probe their microenvironment. These mechanosensitive structures are highly complex in terms of composition and three-dimensional organization. The aim of my thesis is to identify the force-dependent and force-independent elementary events that govern the formation and maturation of FAs. To this end, I have developed an experimental strategy to reconstitute FAs from a minimal set of proteins in order to control molecular composition and determine the key steps in FA function. This work has enabled us to highlight the mechanosensitivity of certain fundamental events. Ultimately, it will provide a better understanding of FAs and how they are deregulated in cancer cells.
Integrin adhesion sites, biomimetic reconstitution, mechanosensibility, integrin activation, super-resolution microscopy, single particle tracking
– Orré T, Joly A, Karatas Z, Kastberger B, Cabriel C, Böttcher RT, Lévêque-Fort S, Sibarita JB, Fässler R, Wehrle-Haller B, Rossier O, Giannone G. Molecular motion and tridimensional nanoscale localization of kindlin control integrin activation in focal adhesions. Nat Commun. 2021 May 25;12(1):3104. doi: 10.1038/s41467-021-23372-w. PMID: 34035280; PMCID: PMC8149821.