SINGLE MOLECULAR NANOSCOPIC IMAGING ON LIVING CELLS

活细胞的单分子纳米成像

基本信息

批准号：
10043309
负责人：
Yang Zhao
金额：
$ 23.79万
依托单位：
UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10043309
关键词：
Analytical Chemistry Area Atomic Force Microscopy Binding Binding Sites Biological Markers Biological Process Biology Cell membrane Cell surface Cells Chemicals Circular Dichroism Circular Dichroism Spectroscopy Coupled DNA Detection Development Disease Exhibits Glycoproteins Goals Handedness Image Imaging Device Ion Channel Label Light Maps Measurement Measures Membrane Membrane Proteins Microscopic Molecular Molecular Conformation Molecular Weight Nanoscopy Nanotechnology Nature Neoplasm Metastasis Optics Outcome Pharmacologic Substance Photons Physicians Property Proteins Receptor Cell Research Resolution Scanning Scanning Probe Microscopes Signal Transduction Specimen Speed Structure System Techniques Therapeutic Therapeutic procedure Time Toxic effect Work base cancer biomarkers chiral molecule enantiomer imaging system improved millisecond molecular dynamics monolayer nano nanometer nanometer resolution novel novel strategies plasmonics protein folding sensor single molecule spatiotemporal spectroscopic imaging targeted agent temporal measurement three dimensional structure tool ultraviolet

项目摘要

ABSTRACT In this research, we will demonstrate a proof of concept super-resolution circular dichroism nanoscopy imaging tool that can map the spectrum of cell membranes at single molecule level. We will capitalize on the high spatial resolution of scanning probe technique and strongly localized field phenomena enhanced by plasmonic chiral metamaterials. We have previously separately demonstrated a planar chiral metamaterial sensor that can measure circular dichroism of chiral molecules with seven orders of magnitude enhancement; and an optical force nanoscopy tool to detect chirality related optical forces from nano-specimen with nanometer spatial resolution. Building upon these previous findings, but very different from the prior work, in this proposal we will fabricate a plasmonic metamaterial on an atomic force microscope (AFM) tip that can locally enhance the chiral optical field-associated forces. This metamaterial-AFM tip can approach the cell membrane in the near field, where the strong optical forces enhanced by the metamaterial interact strongly with the cell membrane molecules. The change of these forces will be detected again by the AFM tip where circular dichroism of the targeting molecules can be de-convoluted. In the long term, this new tool can enable measurements of dynamic conformational changes of membrane molecules such as ion channels, further our understanding of fundamental molecular mechanisms at the single molecular level on living cells.

抽象的在这项研究中，我们将展示概念验证超分辨率圆形二色性纳米镜检查成像可以在单分子水平上绘制细胞膜光谱的工具。我们将利用高扫描探针技术的空间分辨率和等离激元增强的强烈局部现象现象手性超材料。我们以前已经单独证明了一种平面性手性超材料传感器可以测量具有七个数量级增强的手性分子的圆形二色性；和一个光学纳米镜检查工具可检测纳米特征的手性相关的光学作用空间分辨率。基于这些先前的发现，但与先前的工作完全不同，在此提案中我们将在可以局部增强的原子力显微镜（AFM）尖端上制造等离子体超材料手性光场相关力。这种超材料AFM尖端可以接近细胞膜近场，强大的光学力通过超材料与细胞强烈相互作用膜分子。这些力的变化将由圆形的AFM尖端再次检测到靶分子的二分性能可以解散。从长远来看，这个新工具可以启用膜分子（例如离子通道）动态构象变化的测量，进一步了解活细胞单分子水平的基本分子机制。