CAREER: Biological tuning of plasma membrane mixing

职业：质膜混合的生物调节

• 批准号: 1552439
• 负责人: Sarah Veatch
• 金额: $ 100.42万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1552439&HistoricalAwards=false
• 关键词: CAREER; Biological; tuning; plasma; membrane

All animal cells are surrounded by a plasma membrane that defines the outer surface of the cell. Cells control the protein and lipid composition of their plasma membrane to support a broad range of functions, including acting as a sensor of the local cellular environment. For example, the plasma membrane senses and communicates to the cell interior when it is appropriate to grow and divide, if and where the cell should crawl, or when certain compounds or classes of compounds are present in the vicinity. This project will investigate how and why cells adapt their plasma membrane composition in response to several changes in their growth conditions. Many of these sensing functions are thought to depend on how proteins and lipids are organized within the plasma membrane, and the researchers will investigate how both membrane heterogeneity and sensing functions are impacted as cells adjust membrane composition. The long term goals of the project are to discover how cells maintain a heterogeneous membrane, and how this membrane structure contributes to the efficient functioning of the cell. The researchers will communicate their findings through publications, conference presentations, public lectures, development of undergraduate curricula, and outreach to high school students from backgrounds that are under-represented in the physical sciences. The principle investigator will train undergraduate and graduate students for careers in STEM fields.Plasma membranes isolated from intact cells separate into two liquid phases when cooled below room temperature, similar to oil and water in three dimensions. The presence of this phase transition at low temperature predicts the existence of smaller membrane domains at the higher temperatures where cells live in culture. The objective of the research is to directly observe domains in intact cells at growth temperature, and to determine if cells tune their membrane composition to control the physical properties of these domains in order to optimize cellular functions. The research will use conventional cell biological, biochemical, and biophysical techniques as well as cutting edge experimental methods, including super-resolution fluorescence localization microscopy to image the nano-scale organization of membrane components and quantitative lipidomics to detail plasma membrane lipid composition.

所有动物细胞都被限定细胞外表面的质膜包围。 细胞控制其质膜的蛋白质和脂质组成以支持广泛的功能，包括充当局部细胞环境的传感器。例如，质膜感觉到细胞内部何时适合生长和分裂，细胞是否应该爬行以及在哪里爬行，或者某些化合物或某些类别的化合物何时存在于附近。该项目将研究细胞如何以及为什么适应其质膜组成，以应对其生长条件的几个变化。许多这些传感功能被认为取决于蛋白质和脂质在质膜内的组织方式，研究人员将研究细胞调节膜组成时膜异质性和传感功能如何受到影响。该项目的长期目标是发现细胞如何维持异质膜，以及这种膜结构如何有助于细胞的有效功能。研究人员将通过出版物、会议演讲、公开讲座、本科课程的开发以及向来自物理科学领域代表性不足的高中生进行宣传来传播他们的发现。 主要研究者将培养本科生和研究生在STEM领域的职业生涯。从完整细胞中分离出的质膜在冷却到室温以下时会分离成两种液相，类似于三维中的油和水。低温下这种相变的存在预示着细胞在培养物中生活的较高温度下存在较小的膜结构域。该研究的目的是在生长温度下直接观察完整细胞中的结构域，并确定细胞是否调整其膜组成以控制这些结构域的物理特性，从而优化细胞功能。该研究将使用传统的细胞生物学，生物化学和生物物理学技术以及尖端的实验方法，包括超分辨率荧光定位显微镜，以成像膜成分的纳米级组织和定量脂质组学，以详细说明质膜脂质组成。

项目成果

Conditions that Stabilize Membrane Domains Also Antagonize n-Alcohol Anesthesia

• DOI: 10.1016/j.bpj.2016.06.039
• 发表时间: 2016-08-09
• 期刊: BIOPHYSICAL JOURNAL
• 影响因子: 3.4
• 作者: Machta, Benjamin B.;Gray, Ellyn;Veatch, Sarah L.
• 通讯作者: Veatch, Sarah L.