J Am Chem Soc. 2018 May 23;140(20):6226-6230. doi: 10.1021/jacs.8b03459. Epub 2018 May 15.
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.
DNA 在 DNA 功能化纳米颗粒表面上的杂交（例如，以球形核酸 (SNA) 的形式）已知相对于溶液中自由杂交会增强。令人惊讶的是，通过等温滴定量热法，我们揭示了这种增强主要是由焓驱动的，而不是熵驱动的，约为 20 kcal/mol。粗粒分子动力学模拟表明，观察到的焓增强是由于结构上限制了纳米颗粒表面上的 DNA，并防止其采用不利的焓构象，如在溶液情况下观察到的那样。结构限制导致形成更稳定的双链体的想法通过降低双链体在纳米颗粒表面上的受限程度来评估。实验和模拟都证实，当表面结合的双链体受到的限制较少时，即 DNA 表面密度较低或距离纳米颗粒表面较远时，其形成焓接近溶液中线性链形成的较不利的焓。这项工作深入了解了 SNA 最重要和最具启发性的特性之一，并将为依赖于 DNA 功能化表面杂交热力学的材料设计提供信息，包括诊断探针和治疗剂。
