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

合作研究：异质膜组装非脂质成分

• 批准号: 1905600
• 负责人: Sarah Veatch
• 金额: $ 25.31万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 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 2023-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1905600&HistoricalAwards=false
• 关键词: Collaborative; Research; Assembly; non; lipid

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.

非技术摘要与脂质膜偶联的非脂质组分直接相互作用，但也通过膜感受到有效的相互作用。特别是，非脂质成分的相变显着变化时，组件的子集是膜耦合的散装。 一些过去的工作已经探索了这些差异，膜本身是均匀的。 本研究的目的是探索膜和非脂质组分都能够经历溶解性相变的系统。 这些系统代表了新型生物材料，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明确的模型系统中使用热力学模拟和实验：一个结合了在本体中形成液相的聚电解质，第二个利用工程DNA折纸瓦片，当耦合到膜时组装成二维晶格。 脂质膜形成动物细胞与其环境之间的边界，并定义了一些亚细胞区室，如细胞核和线粒体。这些膜主要由脂质、肥皂状分子组成，这些分子自发地形成流体、柔性片，作为大分子或带电分子的边界。 细胞膜还含有嵌入的蛋白质，它们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，并有助于组装拴在膜上的更大结构。 细胞利用这种耦合来传递跨膜信号，或者感知膜特性的化学或机械变化。 该项目从细胞中汲取灵感，开发最小系统，探索这些生物过程的基本概念。 研究人员将探索两个控制良好的带电聚合物系统和拴在膜上的工程DNA折纸瓦片，并将确定膜如何影响非脂质成分的组织和组装，以及非脂质成分的组织如何影响膜。 长期目标是激发能够感知和响应各种环境刺激的新材料。研究人员将通过出版物，会议报告，公开讲座以及将研究纳入本科课程来传达他们的研究结果。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值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

The plasma membrane as an adaptable fluid mosaic

• DOI: 10.1016/j.bbamem.2022.184114
• 发表时间: 2023-01-05
• 期刊: BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
• 影响因子: 3.4
• 作者: Veatch，Sarah L.;Rogers，Nat;Shelby，Sarah A.
• 通讯作者: Shelby，Sarah A.

Surface densities prewet a near-critical membrane

表面密度预润湿近临界膜

• DOI: 10.1073/pnas.2103401118
• 发表时间: 2021
• 期刊: Proceedings of the National Academy of Sciences
• 作者: Rouches, Mason;Veatch, Sarah L.;Machta, Benjamin B.
• 通讯作者: Machta, Benjamin B.

The Membrane Phase Transition Gives Rise to Responsive Plasma Membrane Structure and Function

• DOI: 10.1101/cshperspect.a041395
• 发表时间: 2023-11-01
• 期刊: COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
• 影响因子: 7.2
• 作者: Shelby，Sarah A.;Veatch，Sarah L.
• 通讯作者: Veatch，Sarah L.