Molecular Organization and Transport in Synthetic and Biological Nanopores

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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