The requirements on the eukaryotic cytoskeleton are not only of high complexity, but include demands that are actually contradictory in the first place: While the dynamic character of cytoskeletal structures is essential for the motility of cells, their ability for morphological reorganisations and cell division, the structural integrity of cells relies on the stability of cytoskeletal structures. From a biophysical point of view, this dynamic structure formation and stabilization stems from a self-organisation process that is tightly controlled by the simultaneous and competing function of a plethora of actin binding proteins (ABPs). The ABPs can be classified to regulate (1) the polymerisation and depolymerisation kinetics of the individual filaments, (2) the structure of the network by crosslinking and bundling the filaments and (3) the dynamic reorganisation and contraction mediated by molecular motors.
The major goal is to obtain a sound physical understanding of cellular self organizing principles, by successively increase the complexity of the experimental system in a bottom up approach. Three work packages are defined: (i) the microscopic mechanism of the interaction of ABPs with actin filaments on the treadmilling behaviour of actin. (ii) the effect of confinement, hydrodynamic flow and crosslinking proteins in a 2D high density motility assay and (iii) developing a reconstituted 3D active gel composed of actin filaments and crosslinking molecules. To this end, we will introduce and combine established and new biophysical and biochemical methods and interdisciplinary approaches, with a major emphasis on quantitative imaging and analysis techniques. The outcome of the proposed research will have important consequences and impact in fields ranging way beyond biophysics. Direct implications in rheology, polymer physics, material sciences and cell biology are evident, but also new aspects for the construction of novel biomaterials can be expected.
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