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Engineering a Genetically Encoded Magnetic Protein Crystal

  • Thomas L. Li
    Thomas L. Li
    Department of Chemistry, Stanford University, Stanford, California 94305, United States
    Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California 94305, United States
    More by Thomas L. Li
  • Zegao Wang
    Zegao Wang
    Interdisciplinary Nanoscience Center, Aarhus University, Aarhus 8000, Denmark
    More by Zegao Wang
  • He You
    He You
    School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China
    More by He You
  • Qunxiang Ong
    Qunxiang Ong
    Department of Chemistry, Stanford University, Stanford, California 94305, United States
    More by Qunxiang Ong
  • Vamsi J. Varanasi
    Vamsi J. Varanasi
    Department of Chemistry, Stanford University, Stanford, California 94305, United States
  • Mingdong Dong
    Mingdong Dong
    Interdisciplinary Nanoscience Center, Aarhus University, Aarhus 8000, Denmark
  • Bai Lu
    Bai Lu
    School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China
    More by Bai Lu
  • Sergiu P. Paşca
    Sergiu P. Paşca
    Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California 94305, United States
  • , and 
  • Bianxiao Cui*
    Bianxiao Cui
    Department of Chemistry, Stanford University, Stanford, California 94305, United States
    *Phone: (650) 725-9573. E-mail: [email protected]
    More by Bianxiao Cui
Cite this: Nano Lett. 2019, 19, 10, 6955–6963
Publication Date (Web):September 25, 2019
https://doi.org/10.1021/acs.nanolett.9b02266
Copyright © 2019 American Chemical Society

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    Abstract

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    Magnetogenetics is a new field that leverages genetically encoded proteins and protein assemblies that are sensitive to magnetic fields to study and manipulate cell behavior. Theoretical studies show that many proposed magnetogenetic proteins do not contain enough iron to generate substantial magnetic forces. Here, we have engineered a genetically encoded ferritin-containing protein crystal that grows inside mammalian cells. Each of these crystals contains more than 10 million ferritin subunits and is capable of mineralizing substantial amounts of iron. When isolated from cells and loaded with iron in vitro, these crystals generate magnetic forces that are 9 orders of magnitude larger than the forces from the single ferritin cages used in previous studies. These protein crystals are attracted to an applied magnetic field and move toward magnets even when internalized into cells. While additional studies are needed to realize the full potential of magnetogenetics, these results demonstrate the feasibility of engineering protein assemblies for magnetic sensing.

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    Supporting Information

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    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.nanolett.9b02266.

    • Length measurements, live/dead staining, SDS-PAGE gel, Prussian blue staining, simulations of the magnetic field and field gradient, and images of ftn-PAK4 growth (PDF)

    • Movie S1: demonstration that iron-loaded ftn-PAK4 crystals are attracted to a permanent magnet, while inka-PAK4 crystals are not (AVI)

    • Movie S2: demonstration that the upward movement of ftn-PAK4 crystals ceases when the magnet is removed (AVI)

    • Movie S3: 3D confocal time-lapse of iron-exposed ftn-PAK4 and inka-PAK4 crystals in the magnetic pulling setup (AVI)

    • Movie S4: 3D confocal time-lapse of iron-free ftn-PAK4 and inka-PAK4 crystals in the magnetic pulling setup (AVI)

    • Movie S5: HEK293T cells with ftn-PAK4 and inka-PAK4 crystals being pulled by a magnet (AVI)

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    Cited By

    This article is cited by 19 publications.

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