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

纳米核酸液晶：分层自组装作为益生元选择、模板化和自动催化的途径

• 批准号: 1207606
• 负责人: Noel Clark
• 金额: $ 45万
• 依托单位: University of Colorado at Boulder
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1207606&HistoricalAwards=false
• 关键词: LIQUID; CRYSTALS; NANONUCLEIC; ACIDS; HIERARCHICAL

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.

该奖项由位于博尔德的科罗拉多大学材料研究部的生物材料项目授予，由网络和法规集群（BIO/MCB）共同资助。这项研究的动机是我们最近发现了纳米级核酸（nDNA和nRNA）的多种液晶相，即短至6个碱基对的双链核酸的液晶，这是一类令人兴奋的、未开发的液晶形成分子。该项目的关键是发现在互补和非互补nDNA的混合物中，互补DNA仅存在于LC结构域中。因此，在nDNA液晶相中，双链体的双链化、端对端堆叠以及液晶相排序和分离的耦合步骤产生了仅使可双链化DNA能够进入的结构看门人。进入的分子然后被组织成一种结构，如果通过共价键稳定，则该结构应增强它们的互补性和液晶相稳定性。因此，是否有可能为一个液晶相自催化选择，模板，并复制其组成分子，将是一个主要的研究课题，与多环芳烃的多组分混合物和开发过程，导致LC形成的一个自我选择的分子子集开始的长期目标。如果能证明这一点，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据。该项目将使一组研究生和本科生在核酸生物物理学的一个令人兴奋的新领域的培训。作为推广活动的一部分，研究人员将与工业界合作，研究液晶科学在生物科学、可再生能源和相关领域的应用。研究地球生命起源的研究人员普遍认为，生命的最初痕迹是由短的自我复制的DNA样分子组成的系统，长约30个碱基，从所谓的“原始汤”中出现，这些原始汤由溶液中的小的前生物有机分子组成。这种出现是互补性的“爆炸”，其中互补的小分子，即，它们可以选择性地成对粘在一起，互相寻找，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一个想法，即冷凝成液晶液滴是在这样一个过程中选择互补分子的基本机制。通过添加将短DNA偶联成较长链的化学物质，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，互补性将在选择棒状分子组装体的过程中产生互补性，以促进液晶有序性和相分离。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是由液晶有序化所模板化的。探索的选择和反应机制有望为新型分层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学研究生课程开发，以及夏季研究活动，如教师研究经验和本科生研究经验。西部联盟扩大学生的机会，科学数学和研究转型，和麦克奈尔计划提供本科研究机会，为少数民族和代表性不足的群体是计划与此奖项的活动。