Biomechanics of Complex Microtubule Networks

复杂微管网络的生物力学

• 批准号: 1563280
• 负责人: Michael Vershinin
• 金额: $ 39.8万
• 依托单位: University of Utah
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1563280&HistoricalAwards=false
• 关键词: Biomechanics; Complex; Microtubule; Networks

Humans and many other organisms are comprised of cells which possess a complex biomechanical framework: the cytoskeleton. The composition and internal layout of the cytoskeleton is different from cell to cell. Some differences are purely random but there are also clear systematic architectural differences between various cell types. For example, cells involved in diseases (e.g. cancer) often have markedly different cytoskeleton from cells in a healthy organism. It is currently not clear how different cytoskeletal architectures relate to overall cell biomechanical properties. One of the problems hindering progress has been the inability to reproducibly assemble cytoskeletal networks in a controlled environment. However, a recently developed nano-scale assembly technique allows for exactly this: the longest and least flexible cytoskeletal filaments known as microtubules can now be assembled and manipulated with sufficient flexibility and precision to build structures in a controlled environment which mimic what is seen in cells. Research conducted under this award will use this novel approach to examine the biomechanical properties of a number of key biologically relevant filament architectures. The work will also examine how the biomechanics of microtubule cytoskeleton changes when the architecture is identical but the overall size of the filament structure is varied instead. These measurements together will provide both a big picture view (the role of microtubule network architecture in cellular biomechanics) and small scale perspective (how stress propagates across the network).This research will examine several key microtubule network topologies. A recently demonstrated holographic optical trapping approach will be used to assemble microtubule networks in vitro in 3D. Holographic and ordinary trapping will be used together to manipulate and to probe such networks in situ. For a given network layout, this study will also establish how the biomechanical properties of the model network change with overall scale. Therefore, the extent to which select microtubule network architectures contribute to cellular biomechanics will be established. The role of filaments and cross-links with different mechanical properties will also be quantitatively examined using the same experimental technique.

人类和许多其他生物体都是由细胞组成的，这些细胞具有复杂的生物力学框架：细胞骨架。细胞骨架的组成和内部布局因细胞而异。一些差异是纯粹随机的，但各种细胞类型之间也存在明显的系统结构差异。例如，参与疾病（例如癌症）的细胞通常具有与健康生物体中的细胞显著不同的细胞骨架。目前尚不清楚不同的细胞骨架结构与整体细胞生物力学特性之间的关系。阻碍进展的问题之一是无法在受控环境中可重复地组装细胞骨架网络。然而，最近开发的纳米级组装技术恰恰允许这一点：最长和最不灵活的细胞骨架丝称为微管，现在可以组装和操纵，具有足够的灵活性和精度，以在受控环境中构建结构，模仿细胞中所看到的。在该奖项下进行的研究将使用这种新方法来检查一些关键的生物相关细丝结构的生物力学特性。这项工作还将研究如何微管细胞骨架的生物力学变化时，架构是相同的，但整体大小的细丝结构是不同的。这些测量将提供一个大的图片视图（微管网络结构在细胞生物力学中的作用）和小尺度的观点（应力如何在网络中传播）。本研究将研究几个关键的微管网络拓扑结构。最近展示的全息光学捕获方法将用于组装微管网络在体外的3D。全息和普通捕获将一起使用，以操纵和探测这样的网络在原位。对于给定的网络布局，本研究还将确定模型网络的生物力学特性如何随整体规模变化。因此，选择微管网络架构有助于细胞生物力学的程度将被建立。具有不同机械性能的长丝和交联的作用也将使用相同的实验技术进行定量研究。

项目成果

Custom complex 3D microtubule networks for experimentation and engineering

用于实验和工程的定制复杂 3D 微管网络

• DOI: 10.1117/2.1201608.006690
• 发表时间: 2016
• 期刊: SPIE Newsroom
• 作者: Vershinin, Michael;Bergman, Jared;Doval, Florence
• 通讯作者: Doval, Florence

Cargo navigation across 3D microtubule intersections

• DOI: 10.1073/pnas.1707936115
• 发表时间: 2018-01-16
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Bergman, Jared P.;Bovyn, Matthew J.;Vershinin, Michael D.
• 通讯作者: Vershinin, Michael D.

Differential effects of the dynein-regulatory factor Lissencephaly-1 on processive dynein-dynactin motility

• DOI: 10.1074/jbc.m117.790048
• 发表时间: 2017-07-21
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Gutierrez, Pedro A.;Ackermann, Bryce E.;McKenney, Richard J.
• 通讯作者: McKenney, Richard J.

The Effect of Temperature on Microtubule-Based Transport by Cytoplasmic Dynein and Kinesin-1 Motors

• DOI: 10.1016/j.bpj.2016.08.006
• 发表时间: 2016-09-20
• 期刊: BIOPHYSICAL JOURNAL
• 影响因子: 3.4
• 作者: Hong, Weili;Takshak, Anjneya;Vershinin, Michael
• 通讯作者: Vershinin, Michael

Artificial microtubule cytoskeleton construction, manipulation, and modeling via holographic trapping of network nodes

通过网络节点的全息捕获进行人工微管细胞骨架的构建、操作和建模

• DOI: 10.1117/12.2237231
• 发表时间: 2016
• 期刊: SPIE Proceedings
• 作者: Mohseni, Hooman;Agahi, Massoud H.;Razeghi, Manijeh;Bergman, J.;Doval, F.;Vershinin, M.
• 通讯作者: Vershinin, M.