Mixed and active membranes

混合膜和活性膜

• 批准号: EP/I005439/1
• 负责人: Matthew Turner
• 金额: $ 143.45万
• 依托单位: University of Warwick
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FI005439%2F1
• 关键词: Mixed; active; membranes

In this proposal I describe my plan to attack several important open problems facing our understanding of multi-component, non-equilibrium fluid membranes. In a biological context these often interact with the cytoskeleton of a living cell. I will study how membrane microphase separation is induced by applied forces, such as might arise from coupling to the active cytoskeleton. This model is desperately needed to understand recent data, e.g. for large variations in the local membrane diffusion constant.I also plan to study the regulation and transient adaptation of the membrane tension and pressure of a living cell. I will construct an appropriate non-equilibrium model for the creation of transient bonds between the membrane and the cytoskeleton and use this to establish a self-consistent theory for the steady state, and time variation, of these quantities. Forces generated by molecular motors anchored to the cytoskeleton act on these bonds. The lifetime of the bonds depends on the membrane compliance, which in turn depends on it tension and pressure in a way that can be computed self-consistently. The transient response of the cell following rapid changes in volume or membrane area, can be probed by modern micropipette or tether-pulling experiments. We thereby hope to construct a theory for the active mechanical properties of the cell membrane.I will also work to rigorously test the long standing but untested Saffman-Delbruck theory for membrane diffusion. I will analyse experimental data from Prof Bassereau's group at the Institut Curie. These ongoing experiments have been motivated by our recent theoretical analysis of flows on cylindrical membrane tubes in which we suggest that the controlled variation of tube radius in this geometry may provide the most discriminatory test of the Saffman-Delbruck theory yet proposedI will also study the assembly and dynamics of the FtsZ contractile ring. This protein, a bacterial analogue of tubulin, assembles into fibers that form a ring around dividing bacterial cells. This process involves molecular force generation, fibre self assembly, depolymerisation and membrane-mediated forces, all of which are fields in which I have significant expertise. Very recently model in vitro experiments have studied the role of FtsZ in generating membrane deformation. We plan to repeat similar experiments in membrane vesicles but with the addition of additional vital molecular components, such as FtsA, which plays an important role in associating the FtsZ ring with the membrane. A testable physical model for the action of these dividing rings in generating controlled membrane deformation would be most useful in a field which is of the very highest contemporary interest. There is the hope that this may also have pharmaceutical relevance, e.g. in new antibacterial treatments that target the cell division apparatus.There is an additional element to this proposal which is not included here for reasons of confidentiality.

在这个建议中，我描述了我的计划，以解决我们对多组分非平衡流体膜的理解所面临的几个重要的开放性问题。在生物学背景下，这些经常与活细胞的细胞骨架相互作用。我将研究膜微相分离是如何被外力诱导的，比如可能由与活性细胞骨架的偶联引起的。这个模型是迫切需要了解最近的数据，例如，在当地的膜扩散常数的大的变化。我还计划研究的调节和瞬时适应的膜张力和压力的活细胞。我将构建一个适当的非平衡模型，用于创建膜和细胞骨架之间的瞬态键，并使用此来建立一个自洽的理论，这些量的稳态和时间变化。锚定在细胞骨架上的分子马达产生的力作用于这些键。键的寿命取决于膜的顺应性，这反过来又取决于它的张力和压力的方式，可以计算自洽。细胞在体积或膜面积快速变化后的瞬时反应，可以通过现代微量移液管或牵拉实验来探测。因此，我们希望建立一个理论的积极机械性能的细胞膜。我也将努力严格测试长期存在的，但未经测试的萨夫曼-德尔布鲁克理论的膜扩散。我将分析来自居里研究所巴瑟罗教授小组的实验数据。这些正在进行的实验已经激发了我们最近的理论分析的流动在圆柱形膜管中，我们建议，在这种几何形状的管半径的控制变化可能提供最具歧视性的测试的Saffman-Delbruck理论尚未proposedI还将研究的组装和动态的FtsZ收缩环。这种蛋白质，一种微管蛋白的细菌类似物，组装成纤维，在分裂的细菌细胞周围形成一个环。这个过程涉及分子力的产生，纤维自组装，解聚和膜介导的力量，所有这些都是我拥有重要专业知识的领域。最近的体外模型实验研究了FtsZ在产生膜变形中的作用。我们计划在膜囊泡中重复类似的实验，但添加了额外的重要分子组分，如FtsA，它在将FtsZ环与膜结合中起着重要作用。一个可测试的物理模型，这些分割环在产生受控的膜变形的行动将是最有用的领域，这是非常高的当代利益。希望这也可能具有药物相关性，例如在靶向细胞分裂装置的新的抗菌治疗中。

项目成果

Evolving sensitivity balances Boolean Networks.

不断变化的敏感性平衡了布尔网络。

• DOI: 10.1371/journal.pone.0036010
• 发表时间: 2012
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Luo JX

The topological glass in ring polymers

• DOI: 10.1209/0295-5075/102/58005
• 发表时间: 2013-06-01
• 期刊: EPL
• 影响因子: 1.8
• 作者: Lo, Wei-Chang;Turner, Matthew S.
• 通讯作者: Turner, Matthew S.

A Topologically Driven Glass in Ring Polymers

环形聚合物中的拓扑驱动玻璃

• DOI: 10.48550/arxiv.1510.05625
• 发表时间: 2015
• 作者: Michieletto D

Dynamics of self-threading ring polymers in a gel.

凝胶中自螺纹环聚合物的动力学。

• DOI: 10.1039/c4sm00619d
• 发表时间: 2014
• 期刊: Soft matter
• 影响因子: 3.4
• 作者: Michieletto D

Rings in random environments: sensing disorder through topology.

• DOI: 10.1039/c4sm02324b
• 发表时间: 2014-10
• 期刊: Soft matter
• 影响因子: 3.4
• 作者: D. Michieletto;M. Baiesi;E. Orlandini;M. S. Turner