Supramolecular DNA Structures: From Design to Function

***在过去的6年里，我们的研究在超分子化学和DNA纳米技术领域取得了一些发现。这些包括：******(a) DNA笼，封装治疗药物并选择性地释放它们，只有当它们遇到存在于癌细胞中的分子时，并且这些结构在体外和体内都具有有利的特性。***(b)观察到DNA纳米结构可以用作临时的“印刷机”而不是永久的支架，并且可以将其结构信息转移到金颗粒和聚合物上。这引入了一个概念，即超分子信息可以通过化学方式从一种物质传递到另一种物质。***(c)一种扩展DNA碱基配对代码的替代方法，通过添加一个小的氢键分子，将DNA碱基配对重新编程为“玫瑰”基序。***(d)一类新的单分散和序列控制的聚合物，采用自动化固相DNA合成工具合成。将它们与DNA纳米结构结合，产生了两种材料都无法获得的紧急组装模式。***(e)通过控制可重复使用的成分的添加顺序来构建复杂的DNA结构，从而使用时间控制来实现复杂性。******该提案描述了DNA组装的使用，为两类重要的材料带来前所未有的结构定义和动态特性：合成聚合物和脂质双层。****** DNA纳米结构与脂质双层膜的相互作用。DNA笼在传感、成像和药物输送应用方面具有巨大的潜力。当它们与细胞相互作用时遇到的第一个界面是脂质双层膜，因此了解这一过程对于将它们转化为生物应用至关重要。在本文中，我们研究了DNA纳米结构与脂质双分子层的相互作用，并开发了这些材料的两种应用：作为生物分子检测的膜纳米孔，以及作为介导细胞附着和调节膜曲率的“筏”。******分子“打印”与DNA结构的聚合物。我们将以我们最近的发现为基础，即DNA纳米结构可以用作临时模板，或“印刷机”。人们对增加聚合物纳米结构的复杂性有着极大的兴趣和优雅的方法。然而，DNA的结构定义及其可编程性在聚合物化学中是无与伦比的。我们将描述使用DNA结构作为模板，在2D和3D中将DNA模式共价连接到聚合纳米颗粒上，并通过DNA“成型”策略控制其大小和形状。这导致前所未有的聚合物颗粒以定向方式组装，原子聚集在一起形成分子的方式，从而大大提高了聚合物自组装的控制水平和可编程性。

***Our research during the last 6 years has led to several discoveries in the fields of supramolecular chemistry and DNA nanotechnology. These include:******(a) DNA cages that encapsulate therapeutics and release them selectively, only when they encounter a molecule that is present in cancer cells, and that have favorable in vitro and in vivo properties of these structures. ***(b) the observation that DNA nanostructures can be used as a temporary “printing press” rather than a permanent scaffold, and can transfer their structural information to gold particles and polymers. This introduces the notion that supramolecular information can be chemically transmitted from one material to another. ***(c) an alternative method to expand the DNA base-pairing code, by adding a small hydrogen-bonding molecule that reprograms DNA base-pairing into a “rosette” motif.***(d) a new class of polymers which are monodisperse and sequence-controlled, synthesized by adapting the tools of automated solid-phase DNA synthesis. Combining them with DNA nanostructures leads to emergent assembly modes which could not have been obtained by either material.***(e) the building of complex DNA structures by controlling the order of addition of their components which can then be re-used, thus using temporal control to achieve complexity. ******This proposal describes the use of DNA assembly to bring unprecedented structural definition and dynamic character to two important classes of materials: synthetic polymers and lipid bilayers. ******Interaction of DNA nanostructures with lipid bilayer membranes. DNA cages have tremendous potential for sensing, imaging, and drug delivery applications. The first interface that they encounter when they interact with cells are lipid bilayer membranes, and thus understanding this process is essential to transition them to biological applications. In this proposal, we examine the interaction of DNA nanostructures with lipid bilayers and develop two applications for these materials: as membrane nanopores for biomolecule detection, and as ‘rafts' to mediate cell attachment and tune membrane curvature.******Molecular “Printing” on Polymers with DNA Structures. We will build upon our recent discovery that DNA nanostructures can be used as a temporary template, or a “printing press”. There has been tremendous interest and elegant methods to increase the complexity of polymer nanostructures. However, the structural definition of DNA and its programmability are unmatched in polymer chemistry. We will describe the use of DNA structures as templates to covalently attach DNA patterns to polymeric nanoparticles in 2D- and 3D-, and to control their size and shape with DNA ‘molding' strategies. This results in unprecedented polymer particles that assemble in a directional manner, the way that atoms come together to make molecules, thus dramatically increasing the level of control and programmability in polymer self-assembly.