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arXiv · 1510.01935

Real-time shape approximation and 5-D fingerprinting of single proteins

Erik C. Yusko·Brandon R. Bruhn·Olivia Eggenberger·Jared Houghtaling·Ryan C. Rollings·Nathan C. Walsh·Santoshi Nandivada·Mariya Pindrus·Adam R. Hall·David Sept·Jiali Li·Devendra S. Kalonia·Michael Mayer
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Abstract

This work exploits the zeptoliter sensing volume of electrolyte-filled nanopores to determine, simultaneously and in real time, the approximate shape, volume, charge, rotational diffusion coefficient, and dipole moment of individual proteins. We have developed the theory for a quantitative understanding and analysis of modulations in ionic current that arise from rotational dynamics of single proteins as they move through the electric field inside a nanopore. The resulting multi-parametric information raises the possibility to characterize, identify, and quantify individual proteins and protein complexes in a mixture. This approach interrogates single proteins in solution and determines parameters such as the approximate shape and dipole moment, which are excellent protein descriptors and cannot be obtained otherwise from single protein molecules in solution. Taken together, this five-dimensional characterization of biomolecules at the single particle level has the potential for instantaneous protein identification, quantification, and possibly sorting with implications for structural biology, proteomics, biomarker detection, and routine protein analysis.

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Erik C. Yusko, Brandon R. Bruhn, Olivia Eggenberger, Jared Houghtaling, Ryan C. Rollings, Nathan C. Walsh, Santoshi Nandivada, Mariya Pindrus, Adam R. Hall, David Sept, Jiali Li, Devendra S. Kalonia, Michael Mayer. 2015-08-29. Real-time shape approximation and 5-D fingerprinting of single proteins. https://doi.org/10.1038/nnano.2016.267

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