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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.

摘要在这项研究中，我们将证明概念的超分辨率圆二色性纳米成像这是一个可以在单分子水平上绘制细胞膜光谱的工具。我们会利用等离子体增强扫描探针技术空间分辨率和强局域场现象手性超材料我们之前已经单独展示了平面手性超材料传感器，可以测量手性分子的圆二色性，具有七个数量级的增强; 用于检测来自纳米样品的手性相关光学力的光学力纳米显微镜工具空间分辨率基于这些以前的发现，但与以前的工作非常不同，在本提案中，我们将在原子力显微镜（AFM）尖端上制造一种等离子体超材料，手性光场相关力。这种超材料AFM针尖可以接近细胞膜，近场，其中由超材料增强的强光学力与细胞强烈相互作用膜分子这些力的变化将再次被AFM针尖检测到，靶向分子的二色性可以被去卷积。从长远来看，这种新工具可以使测量膜分子如离子通道的动态构象变化，进一步我们了解活细胞单分子水平的基本分子机制。