A nanoplasmonic molecular ruler for measuring nuclease activity and dna footprinting

Gang L. Liu; Yadong Yin; S. Kunchakarra; Bipasha Mukherjee; Daniele Gerion; Stephen D. Jett; David G. Bear; Joe W. Gray; A. Paul Alivisatos; Luke P. Lee; Fanqing Frank Chen

doi:10.1038/nnano.2006.51

A nanoplasmonic molecular ruler for measuring nuclease activity and dna footprinting

Gang L. Liu, Yadong Yin, S. Kunchakarra, Bipasha Mukherjee, Daniele Gerion, Stephen D. Jett, David G. Bear, Joe W. Gray, A. Paul Alivisatos, Luke P. Lee, Fanqing Frank Chen

Research output: Contribution to journal › Article › peer-review

280 Scopus citations

Abstract

Interactions between nucleic acids and proteins are essential to genetic information processing. The detection of size changes in nucleic acids is the key to mapping such interactions, and usually requires substrates with fluorescent, electrochemical or radioactive labels^1–3. Recently, methods have been developed to tether DNA to highly water-soluble Au nanoparticles^4–8, and nanoparticle pairs linked by DNA have been used to measure nanoscale distances⁹. Here we demonstrate a molecular ruler in which double-stranded DNA is attached to a Au nanoparticle. The change in plasmon resonance wavelength of individual Au–DNA conjugates depends on the length of the DNA and can be measured with subnanometre axial resolution. An average wavelength shift of approximately 1.24 nm is observed per DNA base pair. This system allows for a label-free, quantitative, real-time measurement of nuclease activity and also serves as a new DNA footprinting platform, which can accurately detect and map the specific binding of a protein to DNA.

Original language	English (US)
Pages (from-to)	47-52
Number of pages	6
Journal	Nature nanotechnology
Volume	1
Issue number	1
DOIs	https://doi.org/10.1038/nnano.2006.51
State	Published - Jan 2006
Externally published	Yes

ASJC Scopus subject areas

Bioengineering
Atomic and Molecular Physics, and Optics
Biomedical Engineering
General Materials Science
Condensed Matter Physics
Electrical and Electronic Engineering

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10.1038/nnano.2006.51

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title = "A nanoplasmonic molecular ruler for measuring nuclease activity and dna footprinting",

abstract = "Interactions between nucleic acids and proteins are essential to genetic information processing. The detection of size changes in nucleic acids is the key to mapping such interactions, and usually requires substrates with fluorescent, electrochemical or radioactive labels1–3. Recently, methods have been developed to tether DNA to highly water-soluble Au nanoparticles4–8, and nanoparticle pairs linked by DNA have been used to measure nanoscale distances9. Here we demonstrate a molecular ruler in which double-stranded DNA is attached to a Au nanoparticle. The change in plasmon resonance wavelength of individual Au–DNA conjugates depends on the length of the DNA and can be measured with subnanometre axial resolution. An average wavelength shift of approximately 1.24 nm is observed per DNA base pair. This system allows for a label-free, quantitative, real-time measurement of nuclease activity and also serves as a new DNA footprinting platform, which can accurately detect and map the specific binding of a protein to DNA.",

author = "Liu, {Gang L.} and Yadong Yin and S. Kunchakarra and Bipasha Mukherjee and Daniele Gerion and Jett, {Stephen D.} and Bear, {David G.} and Gray, {Joe W.} and Alivisatos, {A. Paul} and Lee, {Luke P.} and Chen, {Fanqing Frank}",

note = "Funding Information: This work was supported by DARPA, DOD BC045345, NIH R21CA95393, UCSF Prostate Cancer SPORE award (NIH P50 CA89520), and the UCSF Prostate Cancer Center Developmental Research Program, Intel, the Korea Ministry of Science and Technology “21st Century Frontier R&D Program” grant 05K1501-02810. This work was performed under the auspices of the U.S. Dept. of Energy, at the University of California/Lawrence Berkeley National Laboratory under contract no. DE-AC03-76SF00098 and at the University of California/Lawrence Livermore National Laboratory under contract no. W-7405-Eng-48. Supplementary Information accompanies this paper on www.nature.com/naturenanotechnology.",

year = "2006",

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AU - Liu, Gang L.

AU - Yin, Yadong

AU - Kunchakarra, S.

AU - Mukherjee, Bipasha

AU - Gerion, Daniele

AU - Jett, Stephen D.

AU - Bear, David G.

AU - Gray, Joe W.

AU - Alivisatos, A. Paul

AU - Lee, Luke P.

AU - Chen, Fanqing Frank

N1 - Funding Information: This work was supported by DARPA, DOD BC045345, NIH R21CA95393, UCSF Prostate Cancer SPORE award (NIH P50 CA89520), and the UCSF Prostate Cancer Center Developmental Research Program, Intel, the Korea Ministry of Science and Technology “21st Century Frontier R&D Program” grant 05K1501-02810. This work was performed under the auspices of the U.S. Dept. of Energy, at the University of California/Lawrence Berkeley National Laboratory under contract no. DE-AC03-76SF00098 and at the University of California/Lawrence Livermore National Laboratory under contract no. W-7405-Eng-48. Supplementary Information accompanies this paper on www.nature.com/naturenanotechnology.

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N2 - Interactions between nucleic acids and proteins are essential to genetic information processing. The detection of size changes in nucleic acids is the key to mapping such interactions, and usually requires substrates with fluorescent, electrochemical or radioactive labels1–3. Recently, methods have been developed to tether DNA to highly water-soluble Au nanoparticles4–8, and nanoparticle pairs linked by DNA have been used to measure nanoscale distances9. Here we demonstrate a molecular ruler in which double-stranded DNA is attached to a Au nanoparticle. The change in plasmon resonance wavelength of individual Au–DNA conjugates depends on the length of the DNA and can be measured with subnanometre axial resolution. An average wavelength shift of approximately 1.24 nm is observed per DNA base pair. This system allows for a label-free, quantitative, real-time measurement of nuclease activity and also serves as a new DNA footprinting platform, which can accurately detect and map the specific binding of a protein to DNA.

AB - Interactions between nucleic acids and proteins are essential to genetic information processing. The detection of size changes in nucleic acids is the key to mapping such interactions, and usually requires substrates with fluorescent, electrochemical or radioactive labels1–3. Recently, methods have been developed to tether DNA to highly water-soluble Au nanoparticles4–8, and nanoparticle pairs linked by DNA have been used to measure nanoscale distances9. Here we demonstrate a molecular ruler in which double-stranded DNA is attached to a Au nanoparticle. The change in plasmon resonance wavelength of individual Au–DNA conjugates depends on the length of the DNA and can be measured with subnanometre axial resolution. An average wavelength shift of approximately 1.24 nm is observed per DNA base pair. This system allows for a label-free, quantitative, real-time measurement of nuclease activity and also serves as a new DNA footprinting platform, which can accurately detect and map the specific binding of a protein to DNA.

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A nanoplasmonic molecular ruler for measuring nuclease activity and dna footprinting

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