Liquid Crystals of Nanonucleic Acids: Hierarchical Self-Assembly as a Route to Prebiotic Selection, Templating, and Autocatalysis

摘要：生命中遗传信息的记忆和传递是基于核酸（NA）聚合物在溶液中自组装成选择性配对和堆叠的芳香烃纳米片碱基的双柱。进化论最大的谜团之一就是如此壮观的景象是如何在宇宙中出现的。在公认的益生元RNA世界中，低聚物能够进行分子选择、催化和信息传递，它们是由类似的双工配对和堆叠结构构成的，这种结构已经很强大了，似乎来自于一些早期的分子选择和进化模式。研究小组对NA单体和超短低聚物在溶液中的LC相行为的观察表明，实际上不需要聚合来稳定DNA的双碱基配对柱状结构。受此启发，他们开发了一个前rna世界时代的模型，一个“液晶世界”，在这个世界中，双工配对和堆叠进化为自催化分子选择和寡聚化的主要“目的”。选择是通过相分离的NA液晶液滴的分子守门来实现的，这些液滴也作为自身稳定性的促进剂，将选择的短低聚物连接成更长的低聚物。技术摘要：在超短DNA低聚物的液晶相中，双工、双工端到端堆叠、LC排序和相分离的耦合步骤创建了一个结构看门人，优先选择可双工的纳米DNA进入LC。进入的分子被组织成一种流体结构，这种结构可以强烈地促进纳米odna连接成更长的双链，从而稳定LC的顺序，形成一个自催化循环（LC自催化）。拟进行的研究课题包括：获得NA单体双相堆的LC柱状相（选择）；展示了LC在这些相（模板）中辅助单体的连接，并结合了连接对LC有序的影响的研究；研究序列、低聚物长度和多分散性、互补程度对纳米单胞菌中LC自催化的影响，包括(i)末端具有粘附性和（ii）末端具有随机序列的单胞菌，这些单胞菌显著地表现出LC有序形式的互补；采用间歇合成法制备碱基同源物多态溶液，用于NA单体的分子选择实验；纳米na - LC相的缩合机理及缩合对LC自催化的影响研究适用于LC自催化的连接化学研究进展加强对LC自催化结扎产物的评价。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Nontechnical Abstract: The memory and transfer of genetic information in life is based on the self-assembly of nucleic acid (NA) polymers in solution into duplex columns of selectively paired and stacked aromatic hydrocarbon nanosheet bases. One of the great mysteries of evolution is how such a spectacular scenario first appeared in the universe. In the accepted view of a prebiotic RNA world, oligomers which enable molecular selection, catalysis, and information transfer are structured by a similar duplex pairing and stacking scheme which is already robust, appearing to have come from some earlier mode of molecular selection and evolution. The team’s observations of the LC phase behavior of NA monomers and ultra-short oligomers in solution show that polymerization is actually not needed for the stabilization of the duplex base-paired columnar structure of DNA. Motivated by this they have developed a model of a pre-RNA world era, a “liquid crystal world,” in which the duplex pairing and stacking evolves as the primary “purpose” of autocatalytic molecular selection and oligomerization. Selection is achieved by the molecular gatekeeping of phase separated NA liquid crystal droplets, which also serve as promoters of their own stability, templating the ligation of selected short oligomers into longer ones. Technical Abstract: In liquid crystal (LC) phases of ultrashort DNA oligomers, coupled steps of duplexing, end-to-end stacking of duplexes, LC ordering, and phase separation create a structural gatekeeper that preferentially selects duplexable nanoDNA to enter the LC. Molecules that enter are organized into a fluid structure that can strongly promote ligation of the nanoDNA into longer duplexes which, in turn, stabilize the LC ordering, creating an autocatalytic cycle (LC autocatalysis). The proposed research themes include: Obtaining LC columnar phases of duplex stacks of NA monomers (selection); demonstration of LC assisted ligation of monomers in these phases (templating), combined with study of the effect of ligation on LC ordering; Study of the effects of sequence, oligomer length and polydispersity, degree of complementarity on LC autocatalysis in nanoNAs, including those (i) with adhesive ends and (ii) with random sequences, which, remarkably, exhibit the emergence of complimentarity in the form of LC ordering; Employ batch synthesis to prepare polymorphic solutions of base homologs for molecular selection experiments on NA monomers; Advance condensation mechanisms for nanoNA LC phases and study of the effects of condensation on LC autocatalysis; Development of ligation chemistries applicable to LC autocatalysis; Enhanced assessment of the ligation products of LC autocatalysis.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.