Collaborative Research: Mechanics of Reconstituted Self-Organized Contractile Actomyosin Systems

合作研究:重建自组织收缩肌动球蛋白系统的力学

基本信息

项目摘要

Many cellular functions rely on the cytoskeleton, a collection of dynamic networks of biopolymers that provide cells with their mechanical properties and abilities to change shape. These networks have diverse architectures, which often coexist in cells. Although studies of whole cells have enabled characterization of these networks, how they self-organize to give rise to their observed structures and dynamics remains an outstanding question. By reconstituting network structures and dynamics from purified components, this project seeks to define the essential elements for self-organization and enable well-controlled measurements and modeling to probe its mechanisms. To date, such reconstitution studies have largely focused on protein assemblies in bulk solution or on solid supports. However, cells are enclosed by a lipid bilayer membrane, which is thought to be essential for many cellular functions and for the mechanics underlying them. The membrane does not just confine molecular species; it also provides a boundary that can anchor cytoskeletal structures yet deform under typical forces in cells. The project will build on recent technological advances to study protein networks that self-organize into synthetic lipid vesicles. The Broader Impacts of the work include the intrinsic merit of research itself as all cells contain some form of cytoskeleton. Additional activities include training of high school students and their teachers, along with undergraduates and post-doctoral research fellows. The PIs will also contribute to an art installation on synthetic cells that is being developed at the Marine Biological Laboratory at Woods Hole. By systematically characterizing the structures and dynamics accessible to different compositions of cytoskeletal proteins within vesicles, the project will advance understanding of self-organization and force generation by actin networks and the roles membrane confinement and coupling play in these processes. The project will specifically focus on reconstituting features of cell division, in particular the formation and constriction of a contractile ring composed of filamentous actin and the motor protein myosin II, along with additional structural (e.g., anchoring and bundling) proteins. The foundation of our experimental strategy is a powerful platform for reconstituting cytoskeletal networks in giant unilamellar vesicles. This will be paired with coarse-grained simulations of cytoskeletal networks. The project will determine the essential elements for network/ring formation by characterizing the self-organization of mixtures of actin, actin-binding proteins (alpha-actinin, fascin, and/or fimbrin), and motor proteins (myosin and/or a truncated form of it) in the absence of specific membrane interactions. Then, strategies to assemble an actin ring in coexistence with an actin cortex at the membrane will be tested to investigate how membrane binding alters the architecture of actin networks. Finally, patterned motor activation will be used to drive membrane-associated network/ring contraction and vesicle constriction, and the resulting forces will be investigated. To achieve the greatest impact, research, education, and outreach objectives will be closely integrated. This project was co-funded by the Systems and Synthetic Biology, and the Cellular Dynamics and Functions programs, both in the Molecular and Cellular Biosciences Division.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
许多细胞功能依赖于细胞骨架,这是一组动态的生物聚合物网络,为细胞提供机械性能和改变形状的能力。这些网络具有不同的架构,这些架构通常共存于小区中。尽管对整个细胞的研究已经能够描述这些网络的特征,但它们如何自组织起来产生其观察到的结构和动力学仍然是一个悬而未决的问题。通过从纯化的组件重新构建网络结构和动力学,该项目寻求定义自组织的基本元素,并使良好控制的测量和建模能够探索其机制。到目前为止,这类重建研究主要集中在蛋白质在整体溶液或固体载体上的组装。然而,细胞被脂质双层膜包裹着,这被认为是许多细胞功能及其背后的机制所必需的。膜不仅限制了分子物种,它还提供了一个边界,可以固定细胞骨架结构,而不是在细胞内的典型力下变形。该项目将以最新的技术进步为基础,研究自组织成合成脂泡的蛋白质网络。这项工作的更广泛影响包括研究本身的内在价值,因为所有细胞都含有某种形式的细胞骨架。其他活动包括培训高中生和他们的老师,以及本科生和博士后研究员。PI还将为伍兹霍尔海洋生物实验室正在开发的合成细胞艺术装置做出贡献。通过系统地描述囊泡内不同组成的细胞骨架蛋白可获得的结构和动力学,该项目将促进对肌动蛋白网络的自组织和力产生的理解,以及膜限制和耦合在这些过程中所起的作用。该项目将具体侧重于重建细胞分裂的特征,特别是由丝状肌动蛋白和肌球蛋白II以及其他结构(如锚定和捆绑)蛋白质组成的收缩环的形成和收缩。我们实验策略的基础是一个强大的平台,用于在巨大的单层囊泡中重建细胞骨架网络。这将与细胞骨架网络的粗粒度模拟相结合。该项目将通过在没有特定膜相互作用的情况下表征肌动蛋白、肌动蛋白结合蛋白(α-肌动蛋白、筋膜蛋白和/或纤毛蛋白)和马达蛋白(肌球蛋白和/或其截短形式)的混合物的自组织来确定网络/环形成的基本要素。然后,将测试在细胞膜上组装与肌动蛋白皮质共存的肌动蛋白环的策略,以研究膜结合如何改变肌动蛋白网络结构。最后,图案化的马达激活将被用来驱动膜相关的网络/环收缩和囊泡收缩,并将研究由此产生的力。为了实现最大的影响,研究、教育和推广目标将紧密结合在一起。这个项目是由分子和细胞生物科学部的系统和合成生物学以及细胞动力学和功能计划共同资助的。这个奖项反映了NSF的法定使命,并通过使用基金会的智力优势和更广泛的影响审查标准进行评估,被认为值得支持。

项目成果

期刊论文数量(2)
专著数量(0)
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Allen Po-Chih Liu其他文献

Allen Po-Chih Liu的其他文献

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{{ truncateString('Allen Po-Chih Liu', 18)}}的其他基金

Sensing and modulating the chemokine environment with synthetic cells
用合成细胞感知和调节趋化因子环境
  • 批准号:
    10566980
  • 财政年份:
    2023
  • 资助金额:
    $ 50.88万
  • 项目类别:
Development of a mechanosensitive synthetic cell for mediating intercellular communication.
开发用于介导细胞间通讯的机械敏感合成细胞。
  • 批准号:
    10643814
  • 财政年份:
    2020
  • 资助金额:
    $ 50.88万
  • 项目类别:
Development of a mechanosensitive synthetic cell for mediating intercellular communication.
开发用于介导细胞间通讯的机械敏感合成细胞。
  • 批准号:
    10251872
  • 财政年份:
    2020
  • 资助金额:
    $ 50.88万
  • 项目类别:
Development of a mechanosensitive synthetic cell for mediating intercellular communication.
开发用于介导细胞间通讯的机械敏感合成细胞。
  • 批准号:
    10722432
  • 财政年份:
    2020
  • 资助金额:
    $ 50.88万
  • 项目类别:
Development of a mechanosensitive synthetic cell for mediating intercellular communication.
开发用于介导细胞间通讯的机械敏感合成细胞。
  • 批准号:
    10031135
  • 财政年份:
    2020
  • 资助金额:
    $ 50.88万
  • 项目类别:
Development of a mechanosensitive synthetic cell for mediating intercellular communication.
开发用于介导细胞间通讯的机械敏感合成细胞。
  • 批准号:
    10544399
  • 财政年份:
    2020
  • 资助金额:
    $ 50.88万
  • 项目类别:
Reconstituting Biology – a Chart to Minimal Cells
重建生物学——最小细胞图表
  • 批准号:
    2013809
  • 财政年份:
    2020
  • 资助金额:
    $ 50.88万
  • 项目类别:
    Standard Grant
Development of a mechanosensitive synthetic cell for mediating intercellular communication.
开发用于介导细胞间通讯的机械敏感合成细胞。
  • 批准号:
    10396123
  • 财政年份:
    2020
  • 资助金额:
    $ 50.88万
  • 项目类别:
ST2: Programmable Interfaces- Exploring the Intersection of Synthetic Biology, Biomaterials, and Soft Matter
ST2:可编程接口 - 探索合成生物学、生物材料和软物质的交叉点
  • 批准号:
    1939310
  • 财政年份:
    2019
  • 资助金额:
    $ 50.88万
  • 项目类别:
    Standard Grant
ISS: Cellular Mechanotransduction by Osteoblasts in Microgravity
ISS:微重力下成骨细胞的细胞力转导
  • 批准号:
    1927803
  • 财政年份:
    2019
  • 资助金额:
    $ 50.88万
  • 项目类别:
    Standard Grant

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Cell Research (细胞研究)
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    30824808
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    2008
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Research on the Rapid Growth Mechanism of KDP Crystal
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    10774081
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    2007
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  • 项目类别:
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