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Accueil > Coin des étudiants > Stages Prolongeable par une thèse. > Tous les stages.

Exploration of GTPases activity by biosensors in controlled microenvironment

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Understanding how adhesion sites sense varied external cues to modulate downstream signaling networks and cell–ECM force transmission is critical to elucidate the sensory mechanisms underlying invasion and tissue architecture.

Cells perceive their microenvironment by sensing chemical, physical and mechanical cues of extracellular matrix through integrin-based adhesive machinery and actomyosin-based contractility. Integrins are transmembrane mechanoreceptors forming the adhesive core of nano- to micro-scale adhesion sites connecting extracellular matrix to actin cytoskeleton. Actomyosin-based traction force controls integrin clustering, ECM remodeling, cell adhesion and shape. These forces induce changes in cytoskeletal organization, adhesion signaling and gene expression, thereby regulating cell proliferation and differentiation.
Understanding how adhesion sites sense varied external cues to modulate downstream signaling networks and cell–ECM force transmission is critical to elucidate the sensory mechanisms underlying invasion and tissue architecture. The Rho GTPase family was identified as downstream signaling proteins as well as actin regulators, playing therefore a key role in the cellular mechano-response. To better understand how mechanical properties of the environment (matrix composition, rigidity, external forces) influence crucial cellular behaviors (migration, invasion, differentiation), we will measure the activity of several Rho GTPases as a function of different controlled micro-environements. Practically, the extracellular matrix rigidity will be varied by using polyacrylamide gels of different compositions. In collaboration with the MOTIV team (LIPhy), the spatio-temporal activity of G-proteins will be measured with FRET biosensors in different cell lines.

contact : Aurélie Dupont