What Controls the Hybridization Thermodynamics of Spherical Nucleic Acids?

Pratik S. Randeria, Matthew R. Jones, Kevin L. Kohlstedt, Resham J. Banga, Monica Olvera De La Cruz, George C Schatz, Chad A. Mirkin

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

The hybridization of free oligonucleotides to densely packed, oriented arrays of DNA modifying the surfaces of spherical nucleic acid (SNA)-gold nanoparticle conjugates occurs with negative cooperativity; i.e., each binding event destabilizes subsequent binding events. DNA hybridization is thus an ever-changing function of the number of strands already hybridized to the particle. Thermodynamic quantification of this behavior reveals a 3 orders of magnitude decrease in the binding constant for the capture of a free oligonucleotide by an SNA conjugate as the fraction of pre-hybridized strands increases from 0 to ∼30%. Increasing the number of pre-hybridized strands imparts an increasing enthalpic penalty to hybridization that makes binding more difficult, while simultaneously decreasing the entropic penalty to hybridization, which makes binding more favorable. Hybridization of free DNA to an SNA is thus governed by both an electrostatic barrier as the SNA accumulates charge with additional binding events and an effect consistent with allostery, where hybridization at certain sites on an SNA modify the binding affinity at a distal site through conformational changes to the remaining single strands. Leveraging these insights allows for the design of conjugates that hybridize free strands with significantly higher efficiencies, some of which approach 100%.

Original languageEnglish
Pages (from-to)3486-3489
Number of pages4
JournalJournal of the American Chemical Society
Volume137
Issue number10
DOIs
Publication statusPublished - Mar 18 2015

Fingerprint

Nucleic acids
Thermodynamics
Nucleic Acids
DNA
Oligonucleotides
Oligonucleotide Array Sequence Analysis
Static Electricity
Gold
Nanoparticles
Electrostatics

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Randeria, P. S., Jones, M. R., Kohlstedt, K. L., Banga, R. J., Olvera De La Cruz, M., Schatz, G. C., & Mirkin, C. A. (2015). What Controls the Hybridization Thermodynamics of Spherical Nucleic Acids? Journal of the American Chemical Society, 137(10), 3486-3489. https://doi.org/10.1021/jacs.5b00670

What Controls the Hybridization Thermodynamics of Spherical Nucleic Acids? / Randeria, Pratik S.; Jones, Matthew R.; Kohlstedt, Kevin L.; Banga, Resham J.; Olvera De La Cruz, Monica; Schatz, George C; Mirkin, Chad A.

In: Journal of the American Chemical Society, Vol. 137, No. 10, 18.03.2015, p. 3486-3489.

Research output: Contribution to journalArticle

Randeria, PS, Jones, MR, Kohlstedt, KL, Banga, RJ, Olvera De La Cruz, M, Schatz, GC & Mirkin, CA 2015, 'What Controls the Hybridization Thermodynamics of Spherical Nucleic Acids?', Journal of the American Chemical Society, vol. 137, no. 10, pp. 3486-3489. https://doi.org/10.1021/jacs.5b00670
Randeria PS, Jones MR, Kohlstedt KL, Banga RJ, Olvera De La Cruz M, Schatz GC et al. What Controls the Hybridization Thermodynamics of Spherical Nucleic Acids? Journal of the American Chemical Society. 2015 Mar 18;137(10):3486-3489. https://doi.org/10.1021/jacs.5b00670
Randeria, Pratik S. ; Jones, Matthew R. ; Kohlstedt, Kevin L. ; Banga, Resham J. ; Olvera De La Cruz, Monica ; Schatz, George C ; Mirkin, Chad A. / What Controls the Hybridization Thermodynamics of Spherical Nucleic Acids?. In: Journal of the American Chemical Society. 2015 ; Vol. 137, No. 10. pp. 3486-3489.
@article{f2f8ca8ce1954aa38c89f24a2ee1f9a8,
title = "What Controls the Hybridization Thermodynamics of Spherical Nucleic Acids?",
abstract = "The hybridization of free oligonucleotides to densely packed, oriented arrays of DNA modifying the surfaces of spherical nucleic acid (SNA)-gold nanoparticle conjugates occurs with negative cooperativity; i.e., each binding event destabilizes subsequent binding events. DNA hybridization is thus an ever-changing function of the number of strands already hybridized to the particle. Thermodynamic quantification of this behavior reveals a 3 orders of magnitude decrease in the binding constant for the capture of a free oligonucleotide by an SNA conjugate as the fraction of pre-hybridized strands increases from 0 to ∼30{\%}. Increasing the number of pre-hybridized strands imparts an increasing enthalpic penalty to hybridization that makes binding more difficult, while simultaneously decreasing the entropic penalty to hybridization, which makes binding more favorable. Hybridization of free DNA to an SNA is thus governed by both an electrostatic barrier as the SNA accumulates charge with additional binding events and an effect consistent with allostery, where hybridization at certain sites on an SNA modify the binding affinity at a distal site through conformational changes to the remaining single strands. Leveraging these insights allows for the design of conjugates that hybridize free strands with significantly higher efficiencies, some of which approach 100{\%}.",
author = "Randeria, {Pratik S.} and Jones, {Matthew R.} and Kohlstedt, {Kevin L.} and Banga, {Resham J.} and {Olvera De La Cruz}, Monica and Schatz, {George C} and Mirkin, {Chad A.}",
year = "2015",
month = "3",
day = "18",
doi = "10.1021/jacs.5b00670",
language = "English",
volume = "137",
pages = "3486--3489",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "American Chemical Society",
number = "10",

}

TY - JOUR

T1 - What Controls the Hybridization Thermodynamics of Spherical Nucleic Acids?

AU - Randeria, Pratik S.

AU - Jones, Matthew R.

AU - Kohlstedt, Kevin L.

AU - Banga, Resham J.

AU - Olvera De La Cruz, Monica

AU - Schatz, George C

AU - Mirkin, Chad A.

PY - 2015/3/18

Y1 - 2015/3/18

N2 - The hybridization of free oligonucleotides to densely packed, oriented arrays of DNA modifying the surfaces of spherical nucleic acid (SNA)-gold nanoparticle conjugates occurs with negative cooperativity; i.e., each binding event destabilizes subsequent binding events. DNA hybridization is thus an ever-changing function of the number of strands already hybridized to the particle. Thermodynamic quantification of this behavior reveals a 3 orders of magnitude decrease in the binding constant for the capture of a free oligonucleotide by an SNA conjugate as the fraction of pre-hybridized strands increases from 0 to ∼30%. Increasing the number of pre-hybridized strands imparts an increasing enthalpic penalty to hybridization that makes binding more difficult, while simultaneously decreasing the entropic penalty to hybridization, which makes binding more favorable. Hybridization of free DNA to an SNA is thus governed by both an electrostatic barrier as the SNA accumulates charge with additional binding events and an effect consistent with allostery, where hybridization at certain sites on an SNA modify the binding affinity at a distal site through conformational changes to the remaining single strands. Leveraging these insights allows for the design of conjugates that hybridize free strands with significantly higher efficiencies, some of which approach 100%.

AB - The hybridization of free oligonucleotides to densely packed, oriented arrays of DNA modifying the surfaces of spherical nucleic acid (SNA)-gold nanoparticle conjugates occurs with negative cooperativity; i.e., each binding event destabilizes subsequent binding events. DNA hybridization is thus an ever-changing function of the number of strands already hybridized to the particle. Thermodynamic quantification of this behavior reveals a 3 orders of magnitude decrease in the binding constant for the capture of a free oligonucleotide by an SNA conjugate as the fraction of pre-hybridized strands increases from 0 to ∼30%. Increasing the number of pre-hybridized strands imparts an increasing enthalpic penalty to hybridization that makes binding more difficult, while simultaneously decreasing the entropic penalty to hybridization, which makes binding more favorable. Hybridization of free DNA to an SNA is thus governed by both an electrostatic barrier as the SNA accumulates charge with additional binding events and an effect consistent with allostery, where hybridization at certain sites on an SNA modify the binding affinity at a distal site through conformational changes to the remaining single strands. Leveraging these insights allows for the design of conjugates that hybridize free strands with significantly higher efficiencies, some of which approach 100%.

UR - http://www.scopus.com/inward/record.url?scp=84925264731&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84925264731&partnerID=8YFLogxK

U2 - 10.1021/jacs.5b00670

DO - 10.1021/jacs.5b00670

M3 - Article

C2 - 25738968

AN - SCOPUS:84925264731

VL - 137

SP - 3486

EP - 3489

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 10

ER -