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Active self-organization of the actin cytoskeleton driven by molecular motors

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The aim of the Biological Soft Matter group at AMOLF is to understand the physical mechanisms that govern the (active) mechanics of cells. We study in parallel two different model systems of cells. The first approach is to reconstitute artificial cells from purified cytoskeletal proteins inside cell-sized PDMS microchambers or inside liposomes. We can thus dissect the roles of polymer physics, motor proteins, and active filament (de)polymerization. The second approach is to reconstitute artificial tissues by growing cells inside simplified extracellular matrices (collagen or fibrin gels), to study mechanosensing and mechanotransduction. Key technologies are optical microscopy and quantitative image analysis, optical tweezer manipulation, and rheology. In my seminar I will focus on the active self-organization of contractile actin-myosin 2 networks. Myosin II motors assemble into bipolar filaments that slide polar actin filaments (F-actin) past each other as they walk to their plus end. We systematically adjust the myosin activity and processivity and the level of crosslinking, to find out how molecular parameters change the emergent properties (structure and mechanics) of the model cytoskeleton. We show with fluorescence microscopy that the motors generate ring-like actin structures whose size and shape depends both on motor and crosslink density. Myosin accumulates at the center of the actin rings, at the plus ends of the actin filaments, leading to polarity sorting of the actin filaments. Increasing crosslink density enhances the network connectivity and thereby increases the contractility of the network, leading to coarsening and eventually to macroscopic gel contraction. The structure and contractile dynamics in the reconstituted system closely resemble observations in vivo. Using these data, we are starting to build a model relating motor activity on a molecular scale to whole-cell organization and mechanics.

This talk is part of the BSS Formal Seminars series.

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