Direct measurement of the dielectric polarization properties of DNA

Edited by B. Montgomery Pettitt, University of Texas Medical Branch, Galveston, TX, and accepted by the Editorial Board July 18, 2014 (received for review March 27, 2014)
August 18, 2014
111 (35) E3624-E3630

Significance

The strength of DNA–DNA and DNA–ligand electrostatic interactions crucially depends on the electric polarizability of DNA, represented by its dielectric constant. This has remained unknown owing to the lack of experimental techniques able to measure it. Here, we experimentally determined the dielectric constant of double-stranded DNA in a native condensed state inside a single bacteriophage as well as the dielectric constants of the protein shell and tail that compose the viral capsid using scanning force microscopy. We supported the experimental data by theoretically determining the DNA dielectric constant using atomistic simulations. Both approaches yield a dielectric constant of DNA around 8, sensibly higher than commonly assumed, thus revealing a DNA intrinsic property essential for realistic computational description of DNA.

Abstract

The electric polarizability of DNA, represented by the dielectric constant, is a key intrinsic property that modulates DNA interaction with effector proteins. Surprisingly, it has so far remained unknown owing to the lack of experimental tools able to access it. Here, we experimentally resolved it by detecting the ultraweak polarization forces of DNA inside single T7 bacteriophages particles using electrostatic force microscopy. In contrast to the common assumption of low-polarizable behavior like proteins (εr ∼ 2–4), we found that the DNA dielectric constant is ∼8, considerably higher than the value of ∼3 found for capsid proteins. State-of-the-art molecular dynamic simulations confirm the experimental findings, which result in sensibly decreased DNA interaction free energy than normally predicted by Poisson–Boltzmann methods. Our findings reveal a property at the basis of DNA structure and functions that is needed for realistic theoretical descriptions, and illustrate the synergetic power of scanning probe microscopy and theoretical computation techniques.

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Acknowledgments

We thank Nanotec Electronica for technical assistance; D. Esteban-Ferrer, D. Reguera, and E. Torrents for helpful discussions; and Mar Pulido-Cid for technical help in sample preparation. This work was supported by the Spanish Ministerio de Educación y Ciencia under Grants TEC2010-16844, BIO2012-32868, and BFU2011-29038-C02-1, by the Comunidad de Madrid Grant S-2009/MAT-1507, and by an advanced European Research Council Grant (SimDNA). We thank the Barcelona Supercomputing Center for allocating the required computational resources. M.O. is an Institució Catalana de Recerca i Estudis Avançats academia researcher. P.D.D. is a Programa de Desarrollo de las Ciencias Básicas and Sistema Nacional de Investigadores (Agencia Nacional de Investigación e Innovación) researcher.

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Information & Authors

Information

Published in

Go to Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences
Vol. 111 | No. 35
September 2, 2014
PubMed: 25136104

Classifications

Submission history

Published online: August 18, 2014
Published in issue: September 2, 2014

Keywords

  1. DNA–ligand binding
  2. DNA packaging
  3. atomic force microscopy
  4. atomistic simulations
  5. Poisson–Boltzmann equation

Acknowledgments

We thank Nanotec Electronica for technical assistance; D. Esteban-Ferrer, D. Reguera, and E. Torrents for helpful discussions; and Mar Pulido-Cid for technical help in sample preparation. This work was supported by the Spanish Ministerio de Educación y Ciencia under Grants TEC2010-16844, BIO2012-32868, and BFU2011-29038-C02-1, by the Comunidad de Madrid Grant S-2009/MAT-1507, and by an advanced European Research Council Grant (SimDNA). We thank the Barcelona Supercomputing Center for allocating the required computational resources. M.O. is an Institució Catalana de Recerca i Estudis Avançats academia researcher. P.D.D. is a Programa de Desarrollo de las Ciencias Básicas and Sistema Nacional de Investigadores (Agencia Nacional de Investigación e Innovación) researcher.

Notes

This article is a PNAS Direct Submission. B.M.P. is a guest editor invited by the Editorial Board.

Authors

Affiliations

Ana Cuervo1
Department of Structure of Macromolecules, Centro Nacional de Biotecnologia–Consejo Superior de Investigaciones Cientificas, Campus Cantoblanco, 28049 Madrid, Spain;
Pablo D. Dans1
Institute for Research in Biomedicine–Barcelona Supercomputing Center Joint Research Program in Computational Biology, Institute for Research in Biomedicine–Barcelona, 08028 Barcelona, Spain;
José L. Carrascosa
Department of Structure of Macromolecules, Centro Nacional de Biotecnologia–Consejo Superior de Investigaciones Cientificas, Campus Cantoblanco, 28049 Madrid, Spain;
Instituto Madrileño de Estudios Avanzados en Nanociencia, Cantoblanco, 28049 Madrid, Spain;
Modesto Orozco
Institute for Research in Biomedicine–Barcelona Supercomputing Center Joint Research Program in Computational Biology, Institute for Research in Biomedicine–Barcelona, 08028 Barcelona, Spain;
Facultat de Biologia, Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, 08028 Barcelona, Spain;
Gabriel Gomila
Institut de Bioenginyeria de Catalunya, 08028 Barcelona, Spain; and
Departament d’Electrònica, Universitat de Barcelona, 08028 Barcelona, Spain
Laura Fumagalli2 [email protected]
Institut de Bioenginyeria de Catalunya, 08028 Barcelona, Spain; and
Departament d’Electrònica, Universitat de Barcelona, 08028 Barcelona, Spain

Notes

1
A.C. and P.D.D. contributed equally to this work.
2
To whom correspondence should be addressed. Email: [email protected].
Author contributions: J.L.C., M.O., G.G., and L.F. designed research; A.C., P.D.D., J.L.C., and L.F. performed research; A.C. and J.L.C. prepared and characterized the samples; P.D.D. performed molecular dynamic and PBE calculations; L.F. performed dielectric measurements and analyzed the dielectric data; and P.D.D., J.L.C., M.O., G.G., and L.F. wrote the paper.

Competing Interests

The authors declare no conflict of interest.

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    Direct measurement of the dielectric polarization properties of DNA
    Proceedings of the National Academy of Sciences
    • Vol. 111
    • No. 35
    • pp. 12569-12953

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