Tuning Interfacial Biomolecule Interactions with Massively Parallel Nanopore Arrays

使用大规模并行纳米孔阵列调节界面生物分子相互作用

基本信息

批准号：
1704901
负责人：
Matthew Kipper
金额：
$ 41.09万
依托单位：
Colorado State University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-15 至 2021-10-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1704901&HistoricalAwards=false
关键词：
Tuning Interfacial Biomolecule Interactions Massively

项目摘要

DNA stores biological information with a very high density. New tools of genomics and genetic engineering that have emerged over the past 20 years, providing the transformative capabilities to both "read" DNA, and to "write" DNA. New biosensors that diagnose diseases and predict responses to treatments can be based on "reading" DNA, and development of new pest-resistant crops, for example, can be based on "writing" DNA. While DNA is protected when inside living cells, it is relatively unstable when exposed to environments outside of cells. This work will advance our understanding of how DNA interacts with a new class of materials with DNA-sized, nanoscale pores. The chemistry of these pores can be tuned to optimize interactions with DNA, for storage, stability, and for reporting specific chemical binding events. In future work, these materials could be used to develop new biosensors and advanced nanomaterials that could store DNA or transduce mechanical and chemical signals through controlled DNA binding. We will study the interactions of short DNA segments with the surfaces and pores of crosslinked protein crystals, by atomic force microscopy and adsorption isotherm measurements. Diffusion of DNA within nanopores will be characterized by fluorescence microscopy methods. Finally, we will assess the ability of protein crystals to: stabilize guest DNA, couple DNA-pore interactions to ligand binding on the protein crystal surface, and report DNA hybridization through fluorescence.

DNA以非常高的密度存储生物学信息。在过去的20年中出现了基因组学和基因工程的新工具，为“读取” DNA和“写” DNA提供了变革性的能力。诊断疾病并预测对治疗反应的新生物传感器可以基于“读取” DNA，例如，新的耐药作物的发展可以基于“写作” DNA。尽管在活细胞内部进行DNA受到保护，但在暴露于细胞以外的环境时相对不稳定。这项工作将促进我们对DNA如何与新型材料与DNA大小的纳米级孔相互作用的理解。可以调整这些孔的化学性质以优化与DNA的相互作用，以进行储存，稳定性和报告特定的化学结合事件。在未来的工作中，这些材料可用于开发新的生物传感器和晚期纳米材料，这些纳米材料可以通过受控的DNA结合来存储DNA或转导机械和化学信号。我们将通过原子力显微镜和吸附等温线测量来研究短DNA片段与交联蛋白晶体的表面和孔的相互作用。 DNA在纳米孔中的扩散将以荧光显微镜方法为特征。最后，我们将评估蛋白质晶体的能力：稳定来宾DNA，将DNA孔相互作用与蛋白质晶体表面上的配体结合，并通过荧光报告DNA杂交。