Membrane Protein-based Nanostructured Materials (pilot)

诸如量子点纳米颗粒的纳米结构材料已经提供了丰富的新调色板， 生物传感和其他生物医学应用的功能，利用其大小依赖的属性。 这些特性中最突出的是纳米级量子限制效应， 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”与蛋白质能够特异性结合相互作用，用于生物传感， 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质，即整体和外周膜 蛋白质，还没有与发光纳米颗粒连接。在这项拟议的研究中， 这种未开发的生物膜-纳米颗粒混合系统的构建将导致新的传感器， 基于膜蛋白分子识别和活性功能的探针和诊断。 为了使具有活性膜蛋白的纳米结构材料功能化，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，最重要的问题是试图密切复制脂质组成和膜 受体天然微环境的流动性，使得构象变化或二聚化过程 参与天然分子识别。我们的目标是建造一个仿生的， 人工细胞骨架，其中跨膜蛋白质-聚合物生物缀合物提供强的 锚定需要建立稳定的脂质双层与活性膜蛋白到纳米颗粒上。与此 方法，我们的目标是实现完整的，稳定的生物膜沉积到纳米结构上， 尚未被探索的长度尺度。 我们设想生物膜-量子点混合系统的多种应用， 健康包括： 1.基于膜可扩散配体和受体的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。

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.