"Suspended" Bilayers: New Technology to Study the Dynamics of Membrane Structure

“悬浮”双层：研究膜结构动力学的新技术

• 批准号: 7943069
• 负责人: JAMES ROTHMAN
• 金额: $ 47.64万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7943069
• 关键词: Address; Area; Back; Binding; Biological Assay; Caliber; Carbon; Characteristics; Complement; Copper; Deposition; Development; Diffuse; Diffusion; Electron Microscope; Event; Funding; Glass; Goals; Grant; Image; Imagery; Integral Membrane Protein; Investigation; Laboratories; Lateral; Lipid Bilayers; Lipid Binding; Lipids; Literature; Membrane; Membrane Lipids; Membrane Structure and Function; Methods; National Institute of General Medical Sciences; Nature; Polymers; Proteins; Reaction; Reading; Research; Series; Side; Solid; Solutions; Stimulus; Surface; System; Tail; Technology; Testing; Time; Vesicle; abstracting; aqueous; base; insight; meetings; nanofiber; nanoimprinting; new technology; proteoliposomes; research study; single molecule; submicron; time use

DESCRIPTION (provided by applicant): It is the premise of this Challenge Grant that investigations of the dynamics of membrane structure and function would be tremendously facilitated by the development of robust methods for the manufacture of "suspended" bilayers that are surrounded on both sides by aqueous solutions. This application addresses Challenge Area 06-GM-104, Dynamics of membrane structure and function. Current technology consists of "supported" bilayers that are attached to a solid surface. They are inherently non-dynamic, as proteins they contain are generally immobile by nature, and an attached bilayer is not deformable. The proposed research is organized into a series of specific aims, each corresponding to different potential method(s) for generating functional supported bilayers, which we will explore in parallel, to see which one(s) meet the required criteria for a robust mezzanine platform using functional read-outs like lateral diffusion, binding reactions at the single molecule level, and membrane dynamics as exemplified by SNARE-dependent vesicle fusion. By attacking directly the single most critical technological limitation of mezzanine studies of the dynamics of membrane structure and function, and succeeding in producing planar unsupported bilayers containing functional proteins, we can meet the challenge outlined by NIGMS (Challenge Topic 06-GM-104), and jump start a great variety of insights from many laboratories in the field of membrane dynamics. This is a realistic goal within a two year frame, which will have a broad impact on membrane research, and which would not occur without the stimulus funding. PUBLIC HEALTH RELEVANCE: In the proposed project, we aim to generate freestanding (suspended) functional planar bi-layers for the study of membrane dynamics. Existing technology supported on solid surfaces, results in bi-layers where proteins are immobile and which cannot be deformed. By attacking this limitation, we can jump start a great variety of insights from many laboratories in the field of membrane dynamics.

描述（由申请人提供）：这是这项挑战补助金的前提，即通过开发可靠的方法来促进对膜结构和功能动态的调查，从而极大地促进了生产“悬浮”双层的双层，这些双层被水溶液包围在两侧。该应用程序解决了挑战区域06-gm-104，膜结构和功能的动力学。当前的技术由附着在固体表面的“支持”双层组成。它们固有地是非动态的，因为它们所包含的蛋白质通常是固定的，并且附着的双层没有变形。提出的研究被组织成一系列特定目标，每种都与不同的潜在方法相对应，用于产生功能支持的双层，我们将平行探索，以查看哪个符合较强的夹层夹层平台，该标准使用功能读出的功能读取物（如横向扩散）在单个分子层面上进行了互联网和束缚式的反应。通过直接攻击夹层膜结构和功能动态的夹层研究最关键的技术局限性，并成功地生产了含有功能蛋白的平面的无支撑双层的平面，我们可以满足NIGMS所阐述的挑战（挑战主题06-gm-104），并从许多实验室中启动各种各样的实验室动态的互动型，启动各种各样的Membrane Dynameics of Membrane动态。这是两年内的现实目标，这将对膜研究产生广泛的影响，如果没有刺激资金，这将不会发生。 公共卫生相关性：在拟议的项目中，我们旨在为膜动力学研究产生独立（暂停）功能平面双层。现有的技术支持固体表面，导致蛋白质不动并且无法变形的双层层。通过攻击这一限制，我们可以跳到膜动力学领域的许多实验室的各种见解。