Facilitated transport of actin monomer and cytoskeletal remodeling

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All cells move and change shape by continuously taking apart and rebuilding their internal scaffolding, called a cytoskeleton. A great deal is known about how cells remove and replace cytoskeletal pieces. However, a fundamental challenge for the cell is how to recycle the disassembled pieces. A goal of this project is to understand how cells move the newly disassembled parts to new places where they need to be fast enough to change shape in response to external signals. This work will reveal how cells are able to pull themselves apart, move the disassembled pieces to the right place, and put themselves back together every time they move. The work is important because it will reveal basic principals of dynamic reorganization of the entire cell interior. Understanding these principals is essential to learning how to coordinate cytoskeletal remodeling, knowledge that is critical for a variety of applications. Broader Impact activities will include outreach to a local science museum along with helping to build a quantitative biology community in the northwest.Dynamic control of the actin cytoskeleton is fundamental to processes such as motility, division, and polarization. Although decades of research have defined the mechanisms that control the addition of monomers at the front of the cell and removal of monomers at the back, how the cell transports monomer from the back of the network, where it is removed, to the front of the network, where it is added is unknown. This transport process is essential to cell homeostasis, and it is tacitly assumed to be diffusion because it is fast and difficult to measure. The PIs have for the first time directly measured forward monomer transport. From their measurements it is clear that forward monomer transport is faster than diffusion and dependent upon myosin II contraction. The objectives of this study are to identify the mechanism that makes forward transport of actin faster than diffusion and to define the role of myosin II contraction in driving and directing forward transport to remodel the cytoskeleton. These objectives will be achieved by combining biophysical assays, molecular biology, photonics, single molecule imaging, and mathematical/mass transport analysis. This project is expected to identify long-distance transport mechanisms where diffusion is too slow and direct motor coupling is unlikely because of rapid spatial and temporal changes of the intended transport destination.