DNA步行器调控的纳米粒子超晶格

doi:10.6023/A20090426

摘要/Abstract

作为一种精巧的DNA纳米机器, DNA步行器因其优异的可设计性及可编程性在众多研究领域中展示出强大的应用价值. 本工作通过将基于催化发夹组装的双足DNA步行器与DNA功能化的金纳米粒子(即球形核酸)组装相结合, 开发了一种具有时间依赖性的DNA步行器驱动球形核酸恒温有序组装的策略. 以单组分球形核酸组装体系为例, DNA步行器通过发夹催化组装反应驱动在球形核酸表面上随机行走并逐渐产生带有活性粘性末端的DNA杂交结构, 促使球形核酸表面粘性末端间的“键合”速率与其组装速率在时间尺度上保持同步, 从而得到面心立方(FCC)晶型的超晶格结构. 基于类似原理, 作者还构建了一种DNA步行器驱动的双组分球形核酸组装体系并以此得到氯化铯(CsCl)晶型的超晶格结构.

关键词: 动态DNA纳米机器, 双足DNA步行器, 金纳米粒子, 球形核酸组装, 超晶格结构

As a kind of sophisticated dynamic DNA nanomachine, DNA walker has shown powerful application ability in many aspects due to its excellent structural designability and programmability. Taking advantage of stochastic DNA tracks on surface and adaptable DNA outputs of the well-known catalytic hairpin assembly (CHA) circuits, the DNA walkers that move along DNA-coated three-dimensional particle surfaces have attracted much interests. On the other hand, in the field of DNA-mediated nanoparticle assembly, self-assembly of nanoparticles is a thermodynamically driven nonequilibrium process, which is easily trapped at intermediate local free-energy minima, resulting in a disordered structure. Therefore, effective strategies to evade each local free-energy minimum are highly desired. In addition to the traditional annealing strategy, the time-dependent strategy relied on toehold-mediated strand-displacement DNA circuit recently reported by our group has been proven an alternative solution, where interactions between nanoparticles can be tuned in a time-dependent manner for programming dynamic pathway to achieve a free-energy minimum. Through integrating a CHA-based bipedal DNA walker with a DNA-functionalized gold nanoparticle (i.e., spherical nucleic acid; SNA) assembly, a time-dependent strategy for assembly of SNAs programmed by DNA walker at constant temperature was developed in this work. In our strategy, the active sticky ends used for assembly of SNAs can be gradually generated on nanoparticle surface after the walking of the bipedal DNA walker driven by the CHA reaction to induce the synchronization of assembly and bonding between SNAs, thereby obtaining ordered nanoparticle superlattice structure. Take a one-component SNA assembly system for example, the dynamic walking process of the bipedal DNA walker on the surface of SNA was proved to be stable with good walking ability and persistence at first. Then, the SNA assembly kinetics results showed that the bipedal walker concentrations and DNA linker ratios could greatly influence the aggregation of SNA conjugates. Finally, the performance of the integrated SNA assembly system driven by the bipedal DNA walker was investigated under varied concentrations of bipedal walker. In the presence of lower concentrations of the walker strand, the assembly process of SNAs could have a long residence time to switch between the binding and unbinding of the generated sticky ends and achieved a series of near-equilibrium states. Thus, as the interaction between particles grows, the dynamic pathway of nanoparticles assembly can be programmed to achieve a free-energy minimum to form ordered face-centered cubic (FCC) superlattice structure. Based on similar design principle, an asymmetric two-component SNA assembly system programmed by the bipedal DNA walker was constructed to obtain CsCl superlattice structure. Our DNA walker-programmed SNA assembly strategy will have great potential in the creation of functional nanoscale superlattice materials and in the construction of SNA structures with complex phase behaviors.

Key words: dynamic DNA nanomachine, bipedal DNA walker, gold nanoparticle, spherical nucleic acid assembly, superlattice structure

引用此文

郭宜君, 魏冰, 周翔, 姚东宝, 梁好均. DNA步行器调控的纳米粒子超晶格[J]. 化学学报, 2021, 79(2): 192-199.

Yijun Guo, Bing Wei, Xiang Zhou, Dongbao Yao, Haojun Liang. DNA Walker-Programmed Nanoparticle Superlattice[J]. Acta Chimica Sinica, 2021, 79(2): 192-199.

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图/表 7

图1. 由基于催化发夹组装体系的双足DNA步行器调控SNA恒温有序组装的设计示意图.

Figure 1. Schematic illustration of the ordered assembly of SNA programmed by catalytic hairpin assembly-based bipedal DNA walker at constant temperature.

图2. 双足 DNA步行器在SNA表面行走的详细过程和荧光动力学表征. (a)在SNA表面上由CHA反应驱动的DNA步行器的行走机理的详细策略, 其中荧光报告链用于反应信号表征. (b)在不同浓度双足行走链W1存在下体系的实时荧光动力学反应曲线. 该实验中, [SNA]=2 nmol/L, [H1]=200 nmol/L, [H2]=400 nmol/L, [Reporter]=50 nmol/L, 反应温度为25 ℃.

Figure 2. Detailed scheme and performance of the walking process of the bipedal DNA walker on SNA surface. (a) The detailed process for the walking reaction of the DNA walker driven by CHA reaction on SNA surface. The double-stranded fluorescent Reporter is used for signaling. (b) Real-time fluorescence kinetic curves show the reaction efficiency of the system in the presence of varied concentrations of W1. In this experiment, [SNA]=2 nmol/L, [H1]=200 nmol/L, [H2]=400 nmol/L, and [Reporter]=50 nmol/L. The reaction temperature is 25 ℃.

图3. 行走链W1在H1/SNA表面行走的持久性测试. (a)利用FQ-H1策略探测预先固定在H1/SNA表面的W1行走持久性的详细示意图. (b)不同反应状态下体系的荧光泄露曲线. 在该实验中[SNA]=2 nmol/L, [H1]=200 nmol/L, [H2]=400 nmol/L, [FQ-H1]=200 nmol/L, 反应温度为25 ℃.

Figure 3. Investigation of the persistence of W1 on the H1/SNA surface. (a) Detailed scheme of persistence test of W1 on surface of H1/SNA using FQ-H1 strategy. (b) Fluorescence leakage curves of the system under different reaction conditions. In this experiment, [SNA]=2 nmol/L, [H1]=200 nmol/L, [H2]=400 nmol/L, and [FQ-H1]=200 nmol/L. The reaction temperature is 25 ℃.

图4. 不同Toehold长度的双足行走链在H1/SNA表面行走持久性研究. (a)不同Toehold长度行走链行走时, Reporter体系的实时荧光动力学反应曲线. [SNA]=2 nmol/L, [H1]=200 nmol/L, [H2]=400 nmol/L, [Reporter]=50 nmol/L. (b)预先固定在表面的不同Toehold长度的行走链反应时的荧光泄露曲线. 该实验中, [SNA]=2 nmol/L, [H1] =200 nmol/L, [H2]=400 nmol/L, [FQ-H1]=200 nmol/L. 反应温度均为25 ℃.

Figure 4. Study of the persistence ability of the bipedal walker on H1/SNA surface with different toehold lengths. (a) Real-time fluorescence kinetics curves of the Reporter system with different toehold lengths of the walker. [SNA]=2 nmol/L, [H1]=200 nmol/L, [H2]=400 nmol/L, and [Reporter]=50 nmol/L. (b) Fluorescence leakage curves of the primed-walker with different toehold lengths. In this experiment, [SNA]=2 nmol/L, [H1]=200 nmol/L, [H2]=400 nmol/L, and [FQ-H1]=200 nmol/L. The reaction temperature is 25 ℃.

图5. (a) DNA步行器驱动的单组分SNA组装系统示意图. (b) SNA与H1的物质的量比对SNA组装体系反应速率的影响. 其中, [SNA]=3.6 nmol/L, [W3]=20 nmol/L, [H2]=[Complex-A]=2×[H1], 反应温度为25 ℃.

Figure 5. (a) The one-component SNA assembly system programmed by the DNA walker. (b) The influence of molar ratios of SNA and H1 on the effect of SNA assembly. Here, [SNA]=3.6 nmol/L, [W3]=20 nmol/L, and [H2]=[Complex-A]=2×[H1]. The reaction temperature is 25 ℃.

图6. (a)使用热退火策略制备SNA组装结构的SAXS表征结果. 其中, 灰色曲线代表理论计算得到的理想FCC超晶格SAXS图形. (b)在不同W3浓度存在下DNA步行器调控单组分SNA组装体系形成的SNA组装结构的SAXS图形. 其中, [SNA]=3.6 nmol/L, [H1]=80×[SNA], [H2]=[Complex-A]=2×[H1], 反应温度为25 ℃.

Figure 6. (a) SAXS measurements for SNA aggregates assembled using the thermal annealing strategy. The gray curves represent the theoretical SAXS patterns for perfect FCC superlattice. (b) SAXS results for SNA aggregates formed using the DNA walker programmed SNA assembly strategy in the presence of various concentrations of W3. Here, [SNA]=3.6 nmol/L, [H1]=80×[SNA], [H2]=[Complex-A]=2×[H1]. The reaction temperature is 25 ℃.

图7. (a) DNA步行器驱动不对称双组分SNA组装示意图. (b)在不同行走链和两组分SNA物质的量比条件下得到的SNA组装结构的SAXS数据图. 灰色曲线代表计算得到的理想的CsCl 超晶格SAXS图形. 其中, [SNA-1]=3.6 nmol/L, [H1]=80×[SNA-1], [H2]=[Complex-1]=2×[H1], [SNA-2]=1.8 nmol/L (左)、3.6 nmol/L (中)、7.2 nmol/L(右); 反应温度为25 ℃.

Figure 7. (a) Scheme for the assembly of the asymmetric two-component SNA system driven by the DNA walker. (b) SAXS patterns of the SNA structures formed under different ratios of two SNAs and various concentrations of W3. The gray curves represent the theoretical SAXS patterns for perfect CsCl superlattice. Here, [SNA-1]=3.6 nmol/L, [H1]=80×[SNA-1], [H2]=[Complex-1]=2×[H1], [SNA-2]=1.8 nmol/L (left), 3.6 nmol/L (center), 7.2 nmol/L (right). The reaction temperature is 25 ℃.

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