Facilitated transport of actin monomer and cytoskeletal remodeling

所有的细胞通过不断地分解和重建它们的内部支架（称为细胞骨架）来移动和改变形状。 关于细胞如何移除和替换细胞骨架碎片，我们已经知道了很多。 然而，电池面临的一个根本挑战是如何回收分解的碎片。 该项目的目标是了解细胞如何将新拆卸的部件移动到新的地方，在那里它们需要足够快来改变形状以响应外部信号。 这项工作将揭示细胞如何能够将自己分开，将分解的碎片移动到正确的位置，并在每次移动时将自己重新组合在一起。 这项工作很重要，因为它将揭示整个细胞内部动态重组的基本原理。 了解这些原理对于学习如何协调细胞骨架重塑至关重要，这些知识对于各种应用至关重要。更广泛的影响活动将包括外展到当地的科学博物馆沿着与帮助建立一个定量生物学社区在西北部。动态控制肌动蛋白细胞骨架是基本的过程，如运动，分裂和极化。虽然几十年的研究已经确定了控制单体在细胞前部添加和单体在后部去除的机制，但细胞如何将单体从网络的后部（去除单体的地方）运输到网络的前部（添加单体的地方）尚不清楚。 这种转运过程对细胞内稳态是必不可少的，并且由于其快速且难以测量，因此被默认为扩散。 PI首次直接测量了前向单体转运。 从他们的测量结果可以清楚地看出，前向单体运输比扩散快，并依赖于肌球蛋白II收缩。本研究的目的是确定的机制，使肌动蛋白的前向运输速度比扩散和定义的作用，肌球蛋白II收缩驱动和指导前向运输重塑细胞骨架。 这些目标将通过结合生物物理测定、分子生物学、光子学、单分子成像和数学/质量传输分析来实现。 预计该项目将查明远距离迁移机制，在这些机制中，由于预定的迁移目的地在空间和时间上的迅速变化，扩散速度太慢，直接的动力耦合不太可能发生。

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.