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Sensing Single Protein Molecules with Solid-State Nanopores

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Nanopores

Abstract

This chapter is focused on the development of experiments and theory of using solid-state nanopores for sensing single protein molecules in their native and unfolded states. Proteins serve diverse roles such as transport carriers, catalysts, molecular motors, cellular structural support, and others that make life possible. Because of these widely differing roles, proteins have an enormously diverse set of shapes, sizes, and charge structures as compared to polynucleic acids. Solid-state nanopores are particularly suitable for characterizing single protein molecules because they can be fabricated with adjustable dimensions and are stable under conditions that denature proteins. This chapter describes the nanopore experimental setup, signal recording, data analysis, and basic principles related to the experiments and the theory connecting the electrical signal with the properties of proteins. Examples of experimental results illustrate the ability of solid-state nanopores to differentiate proteins in their folded and unfolded states. Native-state protein nanopore translocation follows biased one-dimensional diffusion of charged particles that is sensitive to size and electrical charge. Due to the heterogeneous charge sequence of polypeptides, unfolded proteins obey a coupled electrophoretic and thermally activated process that is sequence specific. The chapter concludes with a discussion of future directions and open challenges for single protein characterization using solid-state nanopores.

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Acknowledgments

We thank Professor J. Golovchenko and Harvard nanopore group for nanopore fabrication, Ryan Rollings, Edward W. Graef Jr., Denis F. Tita, and Errol Porter for nanopore fabrication and characterization. We acknowledge the funding support provided by NHGRI/NIH R21HG003290, NHGRI/NIH R21HG00477, NSF/MRSEC 080054, ABI-111/710, and NIH R01GM071684 to DST.

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Authors and Affiliations

  1. Department of Physics, University of Arkansas, 226 Physics Bldg., Fayetteville, AR, 72701, USA

    Jiali Li

Authors
  1. Bradley Ledden
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  2. Daniel Fologea
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  3. David S. Talaga
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  4. Jiali Li
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Correspondence to Jiali Li .

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Editors and Affiliations

  1. Department of Electrical Engineering, Nanotechnology Research and Teaching Fac, University of Texas at Arlington, S. Cooper Street, Arlington, 76019-0119, Texas, USA

    Samir M. Iqbal

  2. Department of Electrical and Computer En, University of Illinois at Urbana-Champai, N. Wright Street 208, Urbana, 61820, Illinois, USA

    Rashid Bashir

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Ledden, B., Fologea, D., Talaga, D.S., Li, J. (2011). Sensing Single Protein Molecules with Solid-State Nanopores. In: Iqbal, S., Bashir, R. (eds) Nanopores. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-8252-0_6

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  • DOI: https://doi.org/10.1007/978-1-4419-8252-0_6

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