Investigation of Protein Transport in Functionalized Polymeric Nanopores

在化学系化学测量与成像（CMI）项目的支持下，伊利诺伊理工学院的关希云教授和他的研究小组正在研究功能化聚合物纳米孔中的蛋白质转运。分子通过通道和孔隙的易位对生物系统的跨膜运输至关重要。Guan团队将专注于研究蛋白质与聚对苯二甲酸乙酯（PET）薄膜合成纳米孔之间的相互作用，并开发新的策略来提高PET纳米孔的分辨率和灵敏度，扩大其应用范围。这项工作的结果有可能促进对PET纳米孔系统的理解，并为PET纳米孔随机传感器的严格设计提供见解。这项提议的研究有可能对各种领域产生广泛的影响，例如生物材料、生物传感、纳米技术和电化学。该项目为研究生、本科生和高中生提供了独特的研究机会，包括积极从代表性不足的群体中招募的个人。在这个研究项目中，伊利诺伊理工学院的Guan团队旨在解决一个瓶颈，即低分辨率和灵敏度，这在过去的十年中限制了PET纳米孔作为单分子随机传感元件在各种应用中的应用。本项目旨在系统考察各种因素对蛋白质与PET纳米孔相互作用的影响，建立PET纳米孔内蛋白质的动力学和热力学性质与孔径、孔内表面功能和物理条件之间的关系。具体目标包括(i)开发一种简单、经济高效、易于创建、稳定、可运输和可重复使用的功能化单轨蚀刻锥形PET纳米孔平台，用于单分子水平的蛋白质表征；（ii）开发一种新的无标签策略来实时研究生物分子的动态结构信息（如构象变化）；（iii）了解各种因素如何影响蛋白质与PET纳米孔相互作用的动力学和热力学性质的机制；（iv）利用现有的物理化学模型或根据需要开发纳米孔系统的新模型来预测纳米孔中蛋白质运输的动力学和热力学性质。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

With support from the Chemical Measurement and Imaging (CMI) Program in the Division of Chemistry, Professor Xiyun Guan and his research team at the Illinois Institute of Technology are investigating protein transport in functionalized polymeric nanopores. Facilitated translocation of molecules through channels and pores is of fundamental importance for transmembrane transport in biological systems. The Guan group will focus their research efforts on investigating the interactions between proteins and synthetic nanoscale-sized pores fabricated in poly-(ethylene terephthalate) (PET) films, and developing new strategies to improve the resolution and sensitivity of PET nanopores and expand their utility. Results from this work have the potential to advance understanding of PET nanopore systems and provide insight into rigorous design of PET nanopore stochastic sensors. The proposed research has the potential to have a broad impact on a variety of areas, such as biomaterials, biosensing, nanotechnology, and electrochemistry. This project provides unique research opportunities for graduate, undergraduate and high-school students, including individuals actively recruited from underrepresented groups. In this research project, the Guan team at the Illinois Institute of Technology aims to address a bottleneck, i.e., poor resolution and sensitivity, which has limited the utility of PET nanopores as single-molecule stochastic sensing elements for various applications in the past decade. The intent of this project is to systematically examine the effects of various factors on the interaction between proteins and the PET nanopores, and establish the relationships between the kinetic and thermodynamic properties of proteins inside a PET nanopore and the pore diameters, pore inner surface functions and physical conditions. Specific objectives include (i) developing a simple, cost-effective, easy to create, stable, transportable and reusable functionalized single-track etched conical-shaped PET nanopore platform for protein characterization at the single molecule level; (ii) developing a new label-free strategy to investigate the dynamic structural information (e.g., conformational change) of biomolecules in real time; (iii) understanding the mechanisms regarding how various factors affect the kinetic and thermodynamic properties of protein interactions with the PET nanopores; and (iv) the using existing physico-chemical models or developing new models, as needed, for nanopore systems to predict the kinetic and thermodynamic properties of protein transport in nanopores.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.