LIQUID CRYSTALS OF NANONUCLEIC ACIDS: HIERARCHICAL SELF-ASSEMBLY AS A ROUTE TO PREBIOTIC SELECTION, TEMPLATING, AND AUTOCATALYSIS

该奖项由科罗拉多大学博尔德分校材料研究部的生物材料计划颁发，由网络与法规集群(BIO/MCB)共同资助。这项研究的动机是我们最近发现了各种纳米级核酸(nDNA和nRNA)的液晶相，即短至6个碱基对的双链核酸液晶，这是一类令人兴奋的、未被探索的液晶形成分子。这个项目的关键是发现在互补和非互补nDNA的混合物中，互补DNA只在LC结构域中被发现。因此，在nDNA液晶相中，双链、双链的端到端堆积以及液晶相有序和分离的耦合步骤创建了只允许双链DNA进入的结构守门人。然后，进入的分子被组织成一种结构，如果通过共价键稳定，应该会增强它们的互补性和液晶相的稳定性。因此，液晶相是否有可能自动催化选择、模板化和复制其组成分子，将是拟议研究的主要主题，长期目标是从多环芳烃的多组分混合物开始，并开发通过自我选择的分子子集形成LC的过程。如果能够证明这一点，那么DNA的线性结构本身就是早期生命中液晶模板的结果，这是一个强有力的论点。该项目将使一批研究生和本科生能够在一个令人兴奋的核酸生物物理学新领域进行培训。作为推广活动的一部分，这位研究人员将在生物科学、可再生能源和相关领域的液晶科学应用领域与工业界合作。研究地球生命起源的研究人员普遍认为，生命的最初遗迹是由短的、自我复制的类似DNA的分子组成的系统，这些分子长达30个碱基，从溶液中的小的益生菌有机小分子的“原始汤”中涌现出来。这种出现是互补性的“爆炸”，即互补的小分子，即可以选择性地成对粘连在一起，相互寻找，聚集在一起，然后通过化学反应形成更大的互补单元。在这个项目中，研究人员提出了这样的想法，即凝聚成液晶液滴是在这种过程中选择互补分子的基本机制。随着化学物质的加入，将短DNA连接成更长的链，缩合将强烈有利于延长液晶液滴中已经互补的DNA。也就是说，在选择棒状分子组装的过程中，互补将滋生互补，以促进液晶秩序和相分离。如果这个猜想是正确的，那么我们将证明DNA的非常线性的聚合物形状在早期生命中就已经被液晶有序所模式化。所探索的选择和反应机理有望为新型层级组织自组装材料开辟道路。拟议的教育活动包括软凝聚态物理研究生课程开发，以及暑期研究活动，如教师研究经验和本科生研究经验。西部联盟扩大学生机会、科学、数学和研究促进转型，以及麦克奈尔项目为少数族裔和代表不足的群体提供本科生研究机会，这些都是该奖项计划开展的活动。

This award by the Biomaterials program in the Division of Materials Research to University of Colorado at Boulder is cofunded by the Networks and Regulations Cluster (BIO/MCB). This research is motivated by our recent discovery of a variety of liquid crystal phases of nanoscale nucleic acids (nDNA and nRNA), i.e. of liquid crystals of duplex nucleic acids as short as 6 base pairs, an exciting, unexplored class of liquid crystal forming molecules. Key to this project is the finding that in a mixture of complementary and noncomplementary nDNA, the complementary DNA is found only in the LC domains. Thus in the nDNA liquid crystal phases, the coupled steps of duplexing, end-to-end stacking of duplexes, and liquid crystal phase ordering and separation create a structural gatekeeper that enables only duplexable DNA to enter. Molecules that do enter are then organized into a structure that if stabilized by covalent links should enhance their complementarity and the liquid crystal phase stability. Thus, whether is it possible for a liquid crystal phase to autocatalytically select, template, and replicate its constituent molecules, will be a principal topic of the proposed research, with the long-term goal of starting with multicomponent mixtures of polycyclic aromatics and developing processes that lead to LC formation by a self-selected subset of molecules. If this can be shown then it is a strong argument that the linear structure of DNA is itself a result of liquid crystal templating in early life. This project will enable the training of a group of graduate and undergraduate students in an exciting new area of nucleic acid biophysics. As part of the outreach activities, the researcher will collaborate with industry in the area of liquid crystal science applications in bioscience, renewable energy and related areas.It is widely believed by researchers studying the origin of life on Earth that life's first vestiges were systems of short self-replicating DNA-like molecules, that got up to about 30 bases long, emerging out of the so-called "primordial soup" of small prebiotic organic molecules in solution. Such an emergence is an "explosion" of complementarity, in which small molecules that are complementary, i.e., that can selectively stick together in pairs, seek each other out, collect together, and then react chemically into larger complementary units. In this project, the researcher has proposed the idea that condensation into liquid crystal droplets is a basic mechanism for selecting complementary molecules in such a process. With the addition of chemistry that couples up the short DNA into longer chains, condensation would strongly favor the lengthening of the already complementary DNA in the liquid crystal droplets. That is, complementarity would breed complementarity, in a process that selects for rod-shaped molecular assemblies, in order to promote liquid crystal order and phase separation. If this conjecture is correct, then we will have shown that the very linear polymer shape of DNA would have been templated by liquid crystal ordering in early life. The selection and reaction mechanisms explored are expected to open avenues to new kinds of hierarchically organized self assembled materials. The proposed educational activities included graduate curriculum development in soft condensed matter physics, and summer research activities such as Research Experience for Teachers, and Research Experience for Undergraduate students. Western Alliance to Expand Student Opportunities, Science Mathematics And Research for Transformation, and McNair programs providing undergraduate research opportunities for minorities and underrepresented groups are planned activities with this award.