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、模板化和自催化的途径

• 批准号: 2005212
• 负责人: Noel Clark
• 金额: $ 55万
• 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: 2020
• 资助国家: 美国
• 起止时间: 2020-12-15 至 2024-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2005212&HistoricalAwards=false
• 关键词: Liquid; Crystals; Nanonucleic; Acids; Hierarchical

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.

非技术摘要：生命中遗传信息的记忆和转移是基于核酸(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的双链柱。进化论最大的谜团之一是这样壮观的场景是如何最初出现在宇宙中的。在公认的益生菌RNA世界的观点中，使分子选择、催化和信息传递成为可能的低聚物是由类似的双链配对和堆积方案构成的，该方案已经很强大，似乎来自于一些早期的分子选择和进化模式。该团队对NA单体和超短低聚物在溶液中的LC相行为的观察表明，DNA的双碱基配对柱状结构的稳定实际上不需要聚合。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”，其中双链配对和堆积演变为自催化分子选择和齐聚的主要“目的”。选择是通过相分离的NA液晶液滴的分子把关实现的，这些液滴也作为自身稳定性的促进剂，将选定的短低聚物连接成较长的低聚物。技术摘要：在超短DNA低聚物的液晶相中，双链、双链的端到端堆积、LC有序和相分离的耦合步骤创建了一个结构守门人，它优先选择可双链的纳米DNA进入LC。进入的分子被组织成一种流体结构，可以强烈地促进纳米DNA连接成更长的双链，这反过来又稳定了LC有序性，创造了一个自催化循环(LC自催化)。建议的研究主题包括：获得NA单体双链堆叠的LC柱状相(选择)；展示这些相中单体的LC辅助连接(模板)，并研究连接对LC有序性的影响；研究序列、齐聚物长度和多分散性、互补程度对纳米NA中LC自催化的影响，包括(I)具有粘性末端的和(II)具有随机序列的，其显著地以LC有序的形式出现互补；采用批量合成来制备碱基同系物的多晶型溶液，用于NA单体的分子选择实验；纳米NA LC相的高级缩合机制和缩合对LC自催化的影响的研究；适用于LC自催化的连接化学的开发；加强对LC自催化的连接产品的评估。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Mono- and bilayer smectic liquid crystal ordering in dense solutions of “gapped” DNA duplexes

• DOI: 10.1073/pnas.2019996118
• 发表时间: 2021-03
• 期刊: Proceedings of the National Academy of Sciences
• 作者: Prabesh Gyawali;R. Saha;Gregory P Smith;M. Salamończyk;Prakash Kharel;S. Basu;Ruipeng Li;M. Fukuto;J. Gleeson;N. Clark;A. Jákli;H. Balci;S. Sprunt

Smectic-B phase and temperature-driven smectic-B to -A transition in concentrated solutions of “gapped” DNA

“带隙”DNA 浓溶液中的近晶 B 相和温度驱动的近晶 B 相到 A 相转变

• DOI: 10.1103/physrevresearch.4.033046
• 发表时间: 2022
• 期刊: Physical Review Research
• 影响因子: 4.2
• 作者: Gyawali, Prabesh;Saha, Rony;Kodikara, Sineth G.;Li, Ruipeng;Fukuto, Masafumi;Gleeson, James T.;Smith, Gregory P.;Clark, Noel A.;Jakli, Antal;Balci, Hamza
• 通讯作者: Balci, Hamza