The Role of Structural Enthalpy in Spherical Nucleic Acid Hybridization

Lam Kiu Fong, Ziwei Wang, George C Schatz, Erik Luijten, Chad A. Mirkin

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

DNA hybridization onto DNA-functionalized nanoparticle surfaces (e.g., in the form of a spherical nucleic acid (SNA)) is known to be enhanced relative to hybridization free in solution. Surprisingly, via isothermal titration calorimetry, we reveal that this enhancement is enthalpically, as opposed to entropically, dominated by ∼20 kcal/mol. Coarse-grained molecular dynamics simulations suggest that the observed enthalpic enhancement results from structurally confining the DNA on the nanoparticle surface and preventing it from adopting enthalpically unfavorable conformations like those observed in the solution case. The idea that structural confinement leads to the formation of energetically more stable duplexes is evaluated by decreasing the degree of confinement a duplex experiences on the nanoparticle surface. Both experiment and simulation confirm that when the surface-bound duplex is less confined, i.e., at lower DNA surface density or at greater distance from the nanoparticle surface, its enthalpy of formation approaches the less favorable enthalpy of duplex formation for the linear strand in solution. This work provides insight into one of the most important and enabling properties of SNAs and will inform the design of materials that rely on the thermodynamics of hybridization onto DNA-functionalized surfaces, including diagnostic probes and therapeutic agents.

Original languageEnglish
Pages (from-to)6226-6230
Number of pages5
JournalJournal of the American Chemical Society
Volume140
Issue number20
DOIs
Publication statusPublished - May 23 2018

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Nucleic Acid Hybridization
Nucleic acids
Nucleic Acids
Enthalpy
Nanoparticles
DNA
Calorimetry
Molecular Dynamics Simulation
Thermodynamics
Titration
Conformations
Molecular dynamics
Computer simulation

ASJC Scopus subject areas

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

Cite this

The Role of Structural Enthalpy in Spherical Nucleic Acid Hybridization. / Fong, Lam Kiu; Wang, Ziwei; Schatz, George C; Luijten, Erik; Mirkin, Chad A.

In: Journal of the American Chemical Society, Vol. 140, No. 20, 23.05.2018, p. 6226-6230.

Research output: Contribution to journalArticle

Fong, Lam Kiu ; Wang, Ziwei ; Schatz, George C ; Luijten, Erik ; Mirkin, Chad A. / The Role of Structural Enthalpy in Spherical Nucleic Acid Hybridization. In: Journal of the American Chemical Society. 2018 ; Vol. 140, No. 20. pp. 6226-6230.
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