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Collaborative Research: Assembly of non-lipid components by heterogeneous membranes

合作研究：异质膜组装非脂质成分

基本信息

批准号：
1905621
负责人：
Benjamin Machta
金额：
$ 22.02万
依托单位：
Yale University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2022-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1905621&HistoricalAwards=false
关键词：
Collaborative Research Assembly non lipid

项目摘要

Non Technical AbstractNon-lipid components coupled to lipid membranes directly interact with one another but also feel effective interactions through the membrane. In particular, phase transitions in non-lipid components vary significantly from the bulk when a subset of components is membrane-coupled. Some past work has explored these differences for membranes that are themselves homogeneous. The objective of the current study is to explore systems in which both membranes and non-lipid components are capable of experiencing miscibility phase transitions. These systems represent novel biomaterials in which membrane-based signals are actuated to non-membrane processes, similar to common themes in signaling pathways. The research will use thermodynamic simulations and experiments in two well-defined model systems: one incorporating polyelectrolytes that form liquid phases in the bulk, and a second utilizing engineered DNA origami tiles that assemble into two dimensional lattices when coupled to membranes. Technical AbstractLipid membranes form boundaries between animal cells and their environments and define some subcellular compartments, such as the cell nucleus and mitochondria. These membranes are primarily made of lipids, soap-like molecules that spontaneously form into fluid, flexible sheets that act as boundaries to large or charged molecules. Cell membranes also contain embedded proteins, which are more complicated molecular machines that carry out an array of biological functions. Within cells, the material properties of the membrane helps to organize some embedded proteins, and contributes to the assembly of larger structures that are tethered to the membrane. Cells take advantage of this coupling to transduce signals across membranes, or to sense chemical or mechanical changes to membrane properties. This project draws inspiration from cells to develop minimal systems to explore the fundamental concepts that underlie these biological processes. Researchers will explore the two well-controlled systems of charged polymers and engineered DNA origami tiles tethered to membranes, and will identify how membranes influence the organization and assembly of non-lipid components and how the organization of non-lipid components impact membranes. The long-term goal is to inspire new materials that can sense and respond to a wide range of environmental stimuli. The researchers will communicate their findings through publications, conference presentations, public lectures, and by incorporating research into undergraduate curricula. The principle investigators will train undergraduate and graduate students for careers in STEM fields.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.

非脂质组分与脂质膜直接相互作用，但也通过膜感受到有效的相互作用。特别是，当一部分组分是膜耦合的时候，非脂质组分的相变与本体有很大的不同。过去的一些工作已经探索了这些膜本身均质的差异。当前研究的目的是探索系统，其中膜和非脂质成分都能够经历混溶相转变。这些系统代表了新的生物材料，其中基于膜的信号被驱动到非膜过程，类似于信号通路中的常见主题。该研究将在两个定义良好的模型系统中使用热力学模拟和实验：一个包含形成液相的聚电解质，另一个使用工程DNA折纸瓦片，当与膜耦合时组装成二维晶格。【技术摘要】脂质膜是动物细胞与周围环境之间的边界，并定义了一些亚细胞区室，如细胞核和线粒体。这些膜主要是由脂质、类皂分子组成的，这些类皂分子会自发形成流体、柔性薄片，充当大分子或带电分子的边界。细胞膜还含有嵌入的蛋白质，这些蛋白质是执行一系列生物功能的更复杂的分子机器。在细胞内，膜的材料特性有助于组织一些嵌入的蛋白质，并有助于连接在膜上的较大结构的组装。细胞利用这种耦合来传递跨膜的信号，或感知膜特性的化学或机械变化。该项目从细胞中汲取灵感，开发最小的系统来探索这些生物过程背后的基本概念。研究人员将探索两种控制良好的系统，即带电聚合物和工程DNA折纸砖系在膜上，并将确定膜如何影响非脂质组分的组织和组装，以及非脂质组分的组织如何影响膜。长期目标是激发能够感知和响应广泛环境刺激的新材料。研究人员将通过出版物、会议报告、公开演讲以及将研究纳入本科课程来交流他们的发现。主要研究人员将培训本科生和研究生在STEM领域的职业生涯。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。