Molecular Organization and Transport in Synthetic and Biological Nanopores

合成和生物纳米孔中的分子组织和运输

• 批准号: 1403058
• 负责人: Igal Szleifer
• 金额: $ 38.61万
• 依托单位: Northwestern University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1403058&HistoricalAwards=false
• 关键词: Molecular; Organization; Transport; Synthetic; Biological

PROPOSAL NO.: 1403058PRINCIPAL INVESTIGATOR: Szleifer, IgalINSTITUTION NAME: Northwestern UniversityTITLE: Molecular Organization and Transport in Synthetic and Biological NanoporesNSF RECEIVE DATE: 10/29/2013Biological and synthetic pores and channels of nanoscale dimensions display unique ionic and protein transport behavior. Nanoporesmodified with supramolecular chemical species (such as polyelectrolyte brushes) have dimensions that are similar to the range of theelectrostatic interactions, and also to the molecular size of the tethered macromolecules. In cells, Nuclear Pore Complexes (NPC)control the transport of species between the cytoplasm and the nucleus using disordered proteins as gate keepers. The competitionbetween molecular and interaction length scales, as well as the geometry of the surfaces, creates interesting possibilities for thecreation of stimuli responsive gates and ion channels and for the fundamental understanding of the interplay between molecularorganization, charge, proteins and nanoparticle transport in nanoconfined environments. The proposed work involves the developmentand application of theoretical approaches that capture the coupling between molecular organization, physical interactions and chemicalequilibrium in order to describe the behavior of the nanopores. Most of the theoretical work will be based on an equilibrium andkinetic molecular theory that has been developed in the group of the PI. Furthermore, comparing the predictions of the moleculartheory with detailed molecular dynamics simulations (when possible) will check the range of applicability of the theory. The proposedwork is separated into two main thrusts: 1) Synthetic nanopores. Understanding how responsive polymers, bulk solution conditionsand the geometry of the nanopore affect the structure and transport of nanoparticles, proteins and small ions through the nanopores.The types of responsive polymers include: weak polyelectrolytes, hydrophobic polymers and pH sensitive zwitterionic polymers. 2)Nuclear Pore Complex. Systematic studies of the role that intrinsic proteins forming the NPC as well as adsorbed proteins have on theability of the pores to gate transport of proteins across the pore. The proposed work is of fundamental importance in the understandingof interfacial properties of responsible materials as well as transport. Moreover, the proposed work will provide guidelines for thedesign of nanoconfined soft materials with a wide range of applications in biosensing, charge or proteins separations, chromatography,drug delivery and microfluidics among others.The understanding of responsive soft materials in confined environments requires multidisciplinary expertise at the interface betweenmaterials science, engineering, physics, chemistry and biology. The proposed work has the dual purpose of: i) fundamentalunderstanding of the coupling between molecular organization, physical interactions and chemical state in confined soft matter and ii)the outcomes of these studies will be used for the molecular design of responsive coatings that lead to desired transport behavior. Thestudy of these complex systems requires the understanding of equilibrium and time dependent properties. The time dependent behaviorspans over many orders of magnitude in time. The proposed work, thus, combines molecular dynamics simulations that are excellentfor short time scales with time dependent molecular theory that enables the study of very long times maintaining a molecular leveldescription of the mixtures. The continued collaboration with the experimental group of Prof. Omar Azzaroni (UNLP, Argentina) andthe theoretical group of Prof. Yitzhak Rabin (Bar-Ilan, Israel) will provide the theoretical work with realistic checks at all stages of thework.The work proposed here will include educational research experiences for graduate and undergraduate students. The PI plans to attractwomen and underrepresented minorities for this project, as he has been successful to do it in the past. The PI will use the resourcesfrom the REU programs administered by Northwestern MRSEC and by the Chemistry of Life Processes Institute. The main findingfrom this research will be included in the undergraduate and graduate courses taught by the PI. The findings from the research will bepublished in peer-reviewed journals and will be posted on the PI's web site. The software developed from this project to apply themolecular theory to complex soft materials will be available for download from the PI's web site and will be aimed for the use bynon-expert due to the multidisciplinary nature of the potential applications of the proposed work

提案编号：1403058主要研究员：Szleifer，Igal机构名称：西北大学标题：合成和生物纳米孔中的分子组织和运输NSF接收日期：10/29/2013纳米级尺寸的生物和合成孔和通道显示出独特的离子和蛋白质运输行为。用超分子化学物质（例如聚电解质刷）修饰的纳米孔的尺寸与静电相互作用的范围相似，也与束缚大分子的分子尺寸相似。在细胞中，核孔复合体 (NPC) 使用无序蛋白质作为看门人来控制细胞质和细胞核之间的物质运输。分子和相互作用长度尺度之间的竞争以及表面的几何形状，为创建刺激响应门和离子通道以及从根本上理解纳米受限环境中分子组织、电荷、蛋白质和纳米粒子传输之间的相互作用创造了有趣的可能性。拟议的工作涉及理论方法的开发和应用，这些方法捕获分子组织、物理相互作用和化学平衡之间的耦合，以描述纳米孔的行为。大部分理论工作将基于 PI 小组开发的平衡和动力学分子理论。此外，将分子理论的预测与详细的分子动力学模拟（如果可能）进行比较将检查该理论的适用范围。拟议的工作分为两个主要方向：1）合成纳米孔。了解响应性聚合物、本体溶液条件和纳米孔的几何形状如何影响纳米颗粒、蛋白质和小离子通过纳米孔的结构和传输。响应性聚合物的类型包括：弱聚电解质、疏水性聚合物和 pH 敏感两性离子聚合物。 2）核孔复合体。系统研究形成 NPC 的内在蛋白质以及吸附蛋白质对孔控制蛋白质跨孔运输的能力的作用。拟议的工作对于理解负责任材料的界面特性以及传输具有根本重要性。此外，拟议的工作将为纳米受限软材料的设计提供指导，该材料在生物传感、电荷或蛋白质分离、色谱、药物输送和微流体等领域具有广泛的应用。对受限环境中响应性软材料的理解需要多学科的专业知识。材料科学、工程、物理、化学和生物学之间的交叉点。拟议的工作具有双重目的：i）从根本上理解受限软物质中分子组织、物理相互作用和化学状态之间的耦合；ii）这些研究的结果将用于响应涂层的分子设计，从而产生所需的结果运输行为。对这些复杂系统的研究需要了解平衡和时间相关特性。时间依赖性行为在时间上跨越多个数量级。因此，所提出的工作将短时间尺度下出色的分子动力学模拟与时间依赖性分子理论相结合，使研究能够在很长的时间内维持混合物的分子水平描述。与 Omar Azzaroni 教授（UNLP，阿根廷）实验组和 Yitzhak Rabin 教授（以色列 Bar-Ilan）理论组的持续合作将为理论工作提供在工作各个阶段的现实检验。这里提出的工作将包括研究生和本科生的教育研究经验。 PI 计划为该项目吸引女性和代表性不足的少数族裔，正如他过去成功做到的那样。 PI 将使用西北大学 MRSEC 和生命过程化学研究所管理的 REU 项目的资源。这项研究的主要发现将包含在 PI 教授的本科生和研究生课程中。研究结果将发表在同行评审期刊上，并将发布在 PI 的网站上。该项目开发的将分子理论应用于复杂软材料的软件可从 PI 网站下载，由于拟议工作潜在应用的多学科性质，该软件将供非专家使用