Final Report Summary - SELFORG (Self Organization in Cytoskeletal Systems)
Within this project we achieved major progress in our understanding of self-organization effects in the cytoskeleton. We were able to reconstitute cytoskeletal networks with varying complexity in the presence of active motors and observe their effect on the shape of lipid vesicles. In the framework of three main work packages we achieved major insights into: (1) the microscopic mechanism of the interaction of ABPs with actin filaments on the treadmilling behavior of actin, (2) the molecular basis of self-organization and pattern formation in 2D high density motility assays and (3) the coupling of topology and activity of cytoskeletal systems confined into vesicles. The scientific challenge was to develop different biochemical well defined model systems in a cross disciplinary approach and at the same time physical high precision measurements and analysis to understand the physical concepts underlying the complex and intricate interplay between the different constituents. We were able to define the inhibitory effect of crosslinking proteins on the treadmilling behavior of actin filaments and link this to the role of fascin within focal adhesion complexes of cells. We identified that binary interactions between propagating filaments are weak. In fact they are too weak to account for the emergence of order in high density motility assay. By this we disovered that the order transition is driven by multiparticle interactions. Furthermore, the addition of actin binding proteins resulted in frozen steady state structures, which we were able to link to the interplay of active transport and growth processes. The interaction of molecular motors with actin filaments turned out to be pH dependent, which we identified to be an effective switch to activate contractile responses of active networks. The encapsulation of active microtubule networks resulted in active vesicles, which showed how topology and activity are intimately linked. The global shape transformations were regular in nature and constituted therefore an activity driven mechanical oscillator. The actomyosin network encapsulation into vesicles turned out to be a promising route to reconstitute the basic active membrane deformations, such as blebbing, protrusions, invaginations and fission. The developed systems set the basis for further progress in rebuilding the activity of living cells from a set of minimal building blocks.