Molecular Organization and Transport in Synthetic and Biological Nanopores

提案编号：1403058 PRINCIPAL研究员：Szleifer，Igal研究人员姓名：西北大学TITLE：合成和生物纳米孔中的分子组织和传输NSF接收日期：10/29/2013纳米尺度的生物和合成孔和通道显示出独特的离子和蛋白质传输行为。用超分子化学物种(如聚电解质刷子)修饰的纳米孔的尺寸与静电相互作用的范围相似，也与被拴系的大分子的分子尺寸相似。在细胞中，核孔复合体(NPC)通过无序的蛋白质作为门把守来控制物种在细胞质和细胞核之间的运输。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，为创造刺激响应门和离子通道以及从根本上理解分子组织、电荷、蛋白质和纳米颗粒在纳米受限环境中的传输之间的相互作用创造了有趣的可能性。这项拟议的工作涉及理论方法的开发和应用，这些方法捕捉分子组织、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。大部分理论工作将建立在PI基团发展起来的平衡和动力学分子理论的基础上。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。这项工作分为两个主要部分：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粒子、蛋白质和小离子的结构和通过纳米孔的传输。响应性聚合物的类型包括：弱聚电解质、疏水性聚合物和pH敏感型两性离子聚合物。2)核孔复合体。对形成鼻咽癌的内在蛋白质以及被吸附的蛋白质对毛孔通过毛孔进行蛋白质运输的能力所起作用的系统研究。这项拟议的工作对于理解负责任材料的界面性质以及运输具有重要意义。此外，拟议的工作将为纳米受限软材料的设计提供指导，这些材料在生物传感、电荷或蛋白质分离、层析、药物输送和微流体等方面具有广泛的应用。理解受限环境中的响应性软材料需要材料科学、工程、物理、化学和生物之间的多学科专业知识。这项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，从而导致预期的传输行为。对这些复杂系统的研究需要了解平衡和依赖时间的性质。这种依赖时间的行为在时间上跨越了许多数量级。因此，拟议的工作将在短时间尺度上表现出色的分子动力学模拟与依赖时间的分子理论相结合，从而能够研究非常长的时间，保持对混合物的分子水平描述。继续与阿根廷UNLP的Omar Azzaroni教授的实验小组和以色列巴伊兰的Yitzhak Rabin教授的理论小组合作，将在工作的各个阶段为理论工作提供现实的检验。PI计划为这个项目吸引两名男性和代表人数不足的少数族裔，因为他过去成功地做到了这一点。PI将使用由西北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括在PI教授的本科生和研究生课程中。这项研究的结果将发表在同行评议的期刊上，并将发布在PI的网站上。从该项目开发的将分子理论应用于复杂软材料的软件将可从PI的网站下载，并将供非专家使用，因为拟议工作的潜在应用具有多学科性质

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