表面修饰DNA材料的研究:理论和模拟

DNA has been gaining a lot of attention in biotechnology and nanotechnology due to its inherent molecular recognition ability. From a biology science perspective, DNA microarray has been widely adopted by the scientific community for a variety of applications. It has revolutionized the way biological research, enabling scientists to measure the expression patterns of thousands of genes in a single experiment. In material science, DNA is a programmable polymer whose physico-chemical properties depend on its nucleotide sequence, which gives rise to many novel materials, such as DNA-functionalized colloidal materials, DNA templates, DNA-based surface assembly. A key feature in all these applications is the use of ssDNA that drive the material assembly through Watson-Crick base pairing with another ssDNA strand to form well-defined double helical DNA. The progress in DNA-based nanotechnology, thus, depends on the understanding thermodynamics and kinetics of DNA on surfaces. However, the study of DNA related systems is not easy due to the complexity rooting in multi components, multi length scales and time scales. As experimental methods for studying dynamics and structure of DNA on surfaces remain to be developed, it is useful to utilize theoretical and computational approaches that allow for prediction, explanation and direct visualization of the processes and interactions involved. Although a wide variety of theoreticcal and computational techniques including analytical theories, atomistic simulations and coarse-grained molecular simulations have been developed, each method has its limitations. We aim to develop a molecular theory, including molecular details as many as possible, to systematically study the thermodynamic and structure behavior of DNA-functionalized materials. The advantage of the molecular theory is the inclusion of specific DNA conformations and the combination of electrostatic interactions and steric repulsions in the system. The molecular theory should culminate in a molecular level description of DNA-functionalized surfaces and a set of general guidelines for experiments.

表面修饰DNA的材料在当今生物和材料等领域有着广泛的应用。如DNA微阵列（基因芯片）掀起了生物实验领域的革命；嫁接DNA的纳米颗粒、DNA纳米碳管等现已成为新型纳米材料的新贵。所有的这些应用都是基于DNA内碱基对的特殊配对原则。与DNA相关的体系一般都具有多组分、复杂的协同相互作用、时间尺度和空间尺度跨度大等特点，给实验和理论研究都带来了很大的难度。我们的目标是发展分子场理论来研究表面修饰DNA材料的热力学性质和结构。分子场理论不同于一般的唯象理论，考虑DNA的各种微观构象，利用自由能极小求出各种构象的几率，为从微观上揭示宏观实验观测量的物理本质提供了可能。DNA层内的静电相互作用和体积拥挤效应在理论框架下自然耦合在一起，体系内各种因素的变化（如盐浓度、pH、DNA浓度等）直接影响到理论结论。我们的理论研究将为DNA相关体系的实验和应用提供重要的理论依据。

表面嫁接高密度DNA的材料在生物工程领域有着特殊的应用前景，然而此类体系中复杂的集体行为成为研究的热点和难点，本项目正是围绕这个课题展开。我们选取了几个体系：首先，我们研究了DNA的杂化行为受到拥挤的环境的影响。我们发现DNA的杂化率并不是随着DNA密度或环境盐浓度的增加而单调变化，而是呈现既有杂化率比单链状态弱的情况，也有强的情况。这正是高密度体系下，静电作用和杂化前后DNA构型熵的差异相互竞争所造成的结果。其次，我们研究了DNA和其他大分子的相互作用。我们与实验课题组合作，研究了末端修饰Cy3的ssDN与PEG层的相互作用。理论计算和实验观测数据定量符合，揭示了体系中各种相互作用所起的效应。再次，我们提出了调控DNA取向的新方案。我们设计了DNA嫁接响应性聚合物材料。当外界条件改变时，会引起聚合物溶解度的突变，导致DNA有效密度的变化，从而引起DNA取向的变化。另外，受到DNA体系的启发，我们对一般高分子的复杂集体行为也开展了研究，取得了不少成果。