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Title: Cell-matrix adhesion and actin cytoskeleton self-organization

Abstract: Focal adhesions (FAs) are mechanosensory integrin-based cell-matrix adhesions formed by cells in vitro and in vivo. They evolve from small nascent adhesions underneath the lamellipodia, and nucleate formation of the actin filament bundles. FAs are peripheral appendages of the actin bundles transducing the signals from the extracellular matrix to the cell contractile machinery and vice versa. Dynamics of the FAs are modulated by the forces exerted on them by the associated actomyosin structures. In search of novel signaling pathways involved in the adhesion-mediated mechanosensing, we identified several protein tyrosine kinases, knockdown of which affected the FAs response to the matrix stiffness. We demonstrated the involvement of these kinases in the regulation of either global cell contractility, or the local contractile activity at the cell periphery.

Upon spreading on planar substrates, fibroblast type cells developed chiral arrays of the actin filament bundles. In the fibroblasts confined to circular adhesive islands, a radially symmetrical system of actin bundles, consisting of alpha-actinin-enriched radial fibers (RFs) and myosin-IIA-enriched transverse fibers (TFs), rearranged spontaneously into a chiral configuration, as a result of the unidirectional tilting of all RFs accompanied by a tangential shift in the retrograde movement of TFs. The handedness of the chiral pattern was regulated by alpha-actinin-1. Experimental observations together with computational modeling, demonstrated how the interactions between RFs nucleated by formins and contractile TFs result in the transition of the actin pattern from radially symmetric to chiral. Such actin-based mechanism could underlie the development of left-right asymmetry in tissues and embryos.  

If you would like to meet with Prof Bershadsky during his visit, please contact Dr Guillaume Charras (g.charras@ucl.ac.uk)

Students and postdocs will have the opportunity for lunch with Prof Beshadsky. Please contact An Tyrrell (a.tyrrell@ucl.ac.uk) to sign up.