TY - JOUR
T1 - The Role of Structural Enthalpy in Spherical Nucleic Acid Hybridization
AU - Fong, Lam Kiu
AU - Wang, Ziwei
AU - Schatz, George C.
AU - Luijten, Erik
AU - Mirkin, Chad A.
N1 - Funding Information:
This material is based upon work supported by the Air Force Office of Scientific Research under awards FA9550-17-1-0348 and FA9550-14-1-0003; the U.S. Department of Commerce, National Institute of Standards and Technology under award 70NANB14H012 as part of the Center for Hierarchical Materials Design (CHiMaD); the National Science Foundation award DMR-1610796; and the Northwestern University Keck Biophysics Facility and a Cancer Center Support Grant (NCI CA060553). L.K.F. gratefully acknowledges the National Science Foundation for a graduate research fellowship and the Center for Computation and Theory of Soft Materials at Northwestern University for a graduate research fellowship.
Publisher Copyright:
© 2018 American Chemical Society.
PY - 2018/5/23
Y1 - 2018/5/23
N2 - 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.
AB - 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.
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U2 - 10.1021/jacs.8b03459
DO - 10.1021/jacs.8b03459
M3 - Article
C2 - 29762017
AN - SCOPUS:85047539015
VL - 140
SP - 6226
EP - 6230
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
SN - 0002-7863
IS - 20
ER -