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

非技术摘要：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烃纳米片碱基的双柱。进化的最大谜团之一是，这样一个壮观的场景最初是如何出现在宇宙中的。在公认的益生元RNA世界的观点中，使分子选择，催化和信息传递成为可能的寡聚体是由类似的双链体配对和堆叠方案构成的，这种方案已经很强大，似乎来自分子选择和进化的早期模式。研究小组对溶液中NA单体和超短寡聚体的LC相行为的观察表明，DNA双链体碱基配对柱状结构的稳定实际上并不需要聚合。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”，其中双链体配对和堆叠演变为自催化分子选择和寡聚化的主要“目的”。选择通过相分离的NA液晶液滴的分子守门来实现，所述相分离的NA液晶液滴也充当其自身稳定性的促进剂，将所选择的短寡聚体连接成较长的寡聚体作为模板。技术摘要：在超短DNA寡聚物的液晶（LC）相中，双链体的双链化、端对端堆叠、LC排序和相分离的耦合步骤产生优先选择可折叠纳米DNA进入LC的结构看门人。进入的分子被组织成流体结构，该流体结构可以强烈地促进纳米DNA连接成更长的双链体，这反过来又稳定LC排序，从而产生自催化循环（LC自催化）。本论文的主要研究内容包括：获得NA单体双层堆叠的液晶柱状相（选择）;在这些阶段中LC辅助单体连接的证明（模板法），结合研究连接对LC有序化的影响;研究序列、寡聚体长度和多分散性、互补程度对纳米NAs中LC自催化的影响，包括那些（i）具有粘性末端的和（ii）具有随机序列的，它们显著地表现出以LC有序形式出现的互补性;采用分批合成制备用于NA单体的分子选择实验的碱基同系物的多晶型溶液;先进的nanoNA LC相的缩合机制以及缩合对LC自催化作用的影响的研究;适用于LC自催化的连接化学的开发; LC自动催化的连接产物的增强评估。该奖项反映了NSF的法定使命，并被认为值得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。

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.