Membrane Protein-based Nanostructured Materials (pilot)

基于膜蛋白的纳米结构材料（试点）

• 批准号: 7574571
• 负责人: M LANE GILCHRIST
• 金额: $ 7.9万
• 依托单位: CITY COLLEGE OF NEW YORK
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7574571
• 关键词: Atomic Force Microscopy; Binding; Biomimetics; Biosensing Techniques; Biotin; Carrier Proteins; Class; Cytoskeleton; Deposition; Development; Diagnostic; Diagnostic Imaging; Dimensions; Dimerization; Electron Microscopy; Enzymes; Facility Construction Funding Category; Fluorescence Spectroscopy; Goals; Hybrids; Image; Integral Membrane Protein; Lead; Length; Ligand Binding; Ligands; Lipid Bilayers; Lipids; Membrane; Membrane Fluidity; Membrane Proteins; Methodology; Methods; Monoclonal Antibodies; Nanostructures; Particle Size; Peripheral; Pharmaceutical Preparations; Pilot Projects; Polymers; Positioning Attribute; Preclinical Drug Evaluation; Process; Property; Proteins; Public Health; Publishing; Quantum Dots; Relative (related person); Research; Risk; Route; Series; Streptavidin; Structure; Surface; System; Technology; Testing; Thick; Work; base; design; imaging probe; innovation; miniaturize; molecular recognition; nanobiosensor; nanoparticle; nanoscale; nanostructured; nanosystems; novel; novel diagnostics; quantum; receptor; research study; self assembly; sensor; single molecule; size; tool

Nanostructured materials such as quantum dot nanoparticles have provided rich new palette of functionalities for biosensing and other biomedical applications that exploit their size-dependent properties. Most prominent among these properties are nanoscale quantum confinement effects that have led to a new class of luminescent nanobiosensors of exceptional photostability and brightness. The functionalization of these nanoparticle "beacons" with proteins capable of specific binding interactions for biosensing and diagnostics has thus far been limited to soluble proteins such as monoclonal antibodies and enzymes. At present, arguably the most important class of cellular proteins, namely integral and peripheral membrane proteins, has not yet been interfaced with luminescent nanoparticles. As initiated in this proposed research, construction of this unexplored class of biomembrane-nanoparticle hybrid systems will lead to new sensors, probes and diagnostics based on membrane protein molecular recognition and active function. To functionalize nanostructured materials with active membrane proteins, the first challenge is to position and stabilize intact lipid bilayers onto surfaces with high curvature relative to the biomembrane thickness. Furthermore, an overriding concern is to attempt to closely replicate the lipid composition and membrane fluidity of the receptor's natural microenvironment so that conformational changes or dimerization processes involved in native molecular recognition can occur. Our goal is to build a biomimetic, nanoparticle-tethered artificial cytoskeleton where membrane-spanning protein-polymer bioconjugates provide the strong anchoring needed to build stable lipid bilayers with active membrane proteins onto nanoparticles. With this method we aim to achieve the deposition of intact, stabilized biomembranes onto nanoscopic structures at length scales that have not yet been explored. We envision multiple applications of biomembrane-quantum dot hybrid systems that could impact public health including: 1. New diagnostics and probes based on dimerization of both membrane diffusible ligands and receptors 2. Nanoparticle targeting and imaging probes based on surface membrane proteins, 3. Highly miniaturized drug screening methods, potentially at the single molecule level.

量子点纳米粒子等纳米结构材料提供了丰富的新调色板 利用其尺寸依赖性特性的生物传感和其他生物医学应用的功能。 这些特性中最突出的是纳米级量子限制效应，它导致了一种新的 一类具有出色光稳定性和亮度的发光纳米生物传感器。的功能化 这些纳米颗粒“信标”与蛋白质能够进行特异性结合相互作用，用于生物传感和 迄今为止，诊断仅限于可溶性蛋白质，例如单克隆抗体和酶。在 目前，可以说是最重要的一类细胞蛋白，即整合膜和外周膜 蛋白质，尚未与发光纳米粒子结合。正如本项拟议研究所发起的那样， 这种未经探索的生物膜-纳米颗粒混合系统的构建将带来新的传感器， 基于膜蛋白分子识别和活性功能的探针和诊断。 为了用活性膜蛋白功能化纳米结构材料，第一个挑战是定位 并将完整的脂质双层稳定在相对于生物膜厚度具有高曲率的表面上。 此外，最重要的问题是尝试精确复制脂质成分和膜 受体自然微环境的流动性，使得构象变化或二聚化过程 可能发生参与天然分子识别。我们的目标是建立一个仿生的、纳米粒子系留的 人工细胞骨架，其中跨膜蛋白聚合物生物共轭物提供了强大的 锚定需要在纳米粒子上构建带有活性膜蛋白的稳定的脂质双层。有了这个 我们的目标是在纳米级结构上沉积完整、稳定的生物膜 尚未探索的长度尺度。 我们设想生物膜-量子点混合系统的多种应用可能会影响公众 健康包括： 1. 基于膜扩散配体和受体二聚化的新诊断和探针 2.基于表面膜蛋白的纳米颗粒靶向和成像探针， 3. 高度小型化的药物筛选方法，可能在单分子水平上。