TY - JOUR
T1 - Role of contacts in long-range protein conductance
AU - Zhang, Bintian
AU - Song, Weisi
AU - Pang, Pei
AU - Lai, Huafang
AU - Chen, Qiang
AU - Zhang, Peiming
AU - Lindsay, Stuart
N1 - Funding Information:
ACKNOWLEDGMENTS. Dr. Quan Qing made many useful suggestions during the course of this work, including the design of reference electrodes that are stable in protein solutions. Ben Miller synthesized all custom reagents. Stephen Johnson suggested the use of a Fab fragment as a control. Ismael Diez-Perez, David Cahen, Tom Moore, and Jan Mol made useful comments on the draft manuscript, and Gabor Vattay and David Beratan contributed to the discussion of the theoretical background. This work was funded in part by the National Human Genome Research Institute (Grant R01 HG009180), Recognition AnalytiX LLC, and the Edward and Nadine Carson Endowment.
Publisher Copyright:
© 2019 National Academy of Sciences. All Rights Reserved.
PY - 2019
Y1 - 2019
N2 - Proteins are widely regarded as insulators, despite reports of electrical conductivity. Here we use measurements of single proteins between electrodes, in their natural aqueous environment to show that the factor controlling measured conductance is the nature of the electrical contact to the protein, and that specific ligands make highly selective electrical contacts. Using six proteins that lack known electrochemical activity, and measuring in a potential region where no ion current flows, we find characteristic peaks in the distributions of measured single-molecule conductances. These peaks depend on the contact chemistry, and hence, on the current path through the protein. In consequence, the measured conductance distribution is sensitive to changes in this path caused by ligand binding, as shown with streptavidin–biotin complexes. Measured conductances are on the order of nanosiemens over distances of many nanometers, orders of magnitude more than could be accounted for by electron tunneling. The current is dominated by contact resistance, so the conductance for a given path is independent of the distance between electrodes, as long as the contact points on the protein can span the gap between electrodes. While there is no currently known biological role for high electronic conductance, its dependence on specific contacts has important technological implications, because no current is observed at all without at least one strongly bonded contact, so direct electrical detection is a highly selective and label-free single-molecule detection method. We demonstrate single-molecule, highly specific, label- and background free-electronic detection of IgG antibodies to HIV and Ebola viruses.
AB - Proteins are widely regarded as insulators, despite reports of electrical conductivity. Here we use measurements of single proteins between electrodes, in their natural aqueous environment to show that the factor controlling measured conductance is the nature of the electrical contact to the protein, and that specific ligands make highly selective electrical contacts. Using six proteins that lack known electrochemical activity, and measuring in a potential region where no ion current flows, we find characteristic peaks in the distributions of measured single-molecule conductances. These peaks depend on the contact chemistry, and hence, on the current path through the protein. In consequence, the measured conductance distribution is sensitive to changes in this path caused by ligand binding, as shown with streptavidin–biotin complexes. Measured conductances are on the order of nanosiemens over distances of many nanometers, orders of magnitude more than could be accounted for by electron tunneling. The current is dominated by contact resistance, so the conductance for a given path is independent of the distance between electrodes, as long as the contact points on the protein can span the gap between electrodes. While there is no currently known biological role for high electronic conductance, its dependence on specific contacts has important technological implications, because no current is observed at all without at least one strongly bonded contact, so direct electrical detection is a highly selective and label-free single-molecule detection method. We demonstrate single-molecule, highly specific, label- and background free-electronic detection of IgG antibodies to HIV and Ebola viruses.
KW - Label-free detection
KW - Molecular electronics
KW - Protein detection
KW - Protein electronics
KW - Single-molecule conductance
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U2 - 10.1073/pnas.1819674116
DO - 10.1073/pnas.1819674116
M3 - Article
C2 - 30846548
AN - SCOPUS:85063957605
SN - 0027-8424
VL - 116
SP - 5886
EP - 5891
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 13
ER -