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Fabrice Senger

Actin dynamics and cell polarity

Published on 15 December 2016

Thesis presented December 15, 2016

Cells sense and integrate a wealth of mechanical and biochemical signals. Signal integration is part of a process, which ensures that cellular functions are in accordance with the extracellular environment. While these processes are highly regulated by biochemical and mechanical signaling and feedback loops, some of the fundamental processes appear to rely on actin cytoskeleton autoassembly giving raise to modules with defined geometrical and mechanical properties. Thus the actin cytoskeleton is a modular architecture, and the modules co-exist within the cell with spatial and functional specificity. The actin cytoskeleton, notably, is involved in cell/matrice signaling. This interaction relies mainly on mechanical signaling involving the actin cytoskeleton, cell/matrix adhesions and the extracellular matrix. To characterize these mechanisms we took advantage of advanced micropatterning techniques, traction force measurements and laser microdissection. By downregulating the expression of α-actinin, one of the main actin crosslinking proteins, we demonstrated that actin cytoskeleton connectivity is essential for proper integration of cell/matrix signalling. Connectivity is essential for rigidity sensing and haptotaxis by ensuring balanced force distribution through the whole cell. Therefore connectivity might be crucial for cell differentiation processes and cellular polarity. Further, in the context of a collaborative project, we have contributed to the characterization of a novel cell adhesion protein, namely, Kank2. We showed, by traction force measurements, that this protein is essential for rigidity sensing. Globally this study demonstrated the implication of Kank2 in cell adhesion maturation and mecanotransduction.

spatial geometry, physical constraints, cell polarity, actin dynamics, cell biology, morphogenesis

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