RUI: Materials Physics with Kinetoplast DNA

RUI：利用 Kinetoplast DNA 进行材料物理

• 批准号: 2105113
• 负责人: Alexander Klotz
• 金额: $ 47.5万
• 依托单位: California State University-Long Beach Foundation
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2105113&HistoricalAwards=false
• 关键词: RUI; Materials; Physics; Kinetoplast; DNA

Non-technical Summary: DNA is best known for its role in carrying genetic information, but DNA molecules can also be used as renewable and biodegradable materials, as well as tools to improve the interface between the human body and synthetic components such as prosthetic implants. Enabling the use of DNA as a biomaterial requires an understanding of its physical properties at the molecular level. Nature produces DNA with complex structures beyond the coils found in our cells: parasites from the trypanosome family, which cause diseases like Sleeping Sickness and Leishmaniasis, have a complex DNA structure called a kinetoplast. A kinetoplast is a linked network of thousands of small circular DNA molecules connected like medieval chainmail armor. Materials with this complex connected structure are not found elsewhere in nature and are difficult to produce artificially, so the properties of this type of material are not well understood. The researchers seek to advance understanding of DNA biomaterials by studying kinetoplasts, learning about their material properties, and investigating how trypanosome cells produce them. Their proposed experiments include studying how chemical conditions change the size of kinetoplasts, stretching the kinetoplasts to measure their material strength and toughness, comparing the kinetoplasts to materials not made of connected rings, and exploring how systems of connected molecules pass through very small holes. All of these aspects are relevant to the biomaterial design process. The significance of this research is that it will provide information needed to expand the use of DNA as a biomaterial and to develop other materials based on molecular linking. The broader impacts of this work involves training a diverse group of students and conducting experiments that will extend to other fields, including the study of two-dimensional materials such as graphene, for which kinetoplasts may serve as a useful model system to bring graphene technology closer to public use, as well as parasitology, where the study of kinetoplasts may allow researchers to better understand ways to prevent the parasite’s reproductive cycle.Technical Summary: In addition to its role in carrying genetic information, DNA has been explored as the basis of renewable and degradable polymer materials, as part of coatings to improve the biocompatibility of implants, and as a substrate for drug delivery. The biomaterial uses of DNA require an understand of its physical properties on the molecular level. The topology of a molecule has a significant effect on its material properties. Kinetoplasts are complex DNA structures found in the mitochondria of trypanosome parasites; each kinetoplast consists of thousands of circular DNA molecules topologically linked in a two-dimensional network akin to medieval chainmail armor. This work focuses on the material properties of kinetoplasts as part of a broader investigation into DNA’s role as a biomaterial and to provide insight into the physics of topologically complex synthetic molecules. The researchers will investigate the effects of solvent chemistry on the equilibrium conformation of kinetoplasts by measuring parameters such as the radius of gyration, which is determined by the competing effects of bending rigidity and thermal fluctuations. Optical tweezers will be used to stretch kinetoplasts, measure their force response and elastic moduli, and quantify the strength of catenane (linked ring) non-covalent bonds. Nanopore sensing will be used to measure the response of kinetoplasts and smaller catenated DNA structures under extreme deformation, which is critical to determine appropriate conditions for biopolymer processing applications. Degradation of the kinetoplasts by restriction enzymes will be used to tune their mechanical properties, ascertain their network topology, and better understand how trypanosomes create these complex structures. As a broader impact, a Pen Pal program will be launched to connect youth from underrepresented groups with student researchers.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：DNA 因其携带遗传信息的作用而闻名，但 DNA 分子也可用作可再生和可生物降解的材料，以及改善人体与假体植入物等合成部件之间界面的工具。要使用 DNA 作为生物材料，需要在分子水平上了解其物理特性。大自然产生的 DNA 具有超出我们细胞中发现的线圈的复杂结构：来自锥虫家族的寄生虫，会导致昏睡病等疾病。利什曼病具有一种称为动质体的复杂 DNA 结构，动质体是由数千个小型圆形 DNA 分子组成的连接网络，就像中世纪的锁子甲一样，具有这种复杂连接结构的材料在自然界中其他地方找不到，并且很难人工生产。研究人员试图通过研究动质体、了解其材料特性以及研究锥虫细胞如何产生它们来加深对 DNA 生物材料的了解。他们提出的实验包括研究化学物质的产生方式。条件改变了动质体的尺寸，拉伸动质体以测量其材料强度和韧性，将动质体与不是由连接环构成的材料进行比较，并探索连接分子系统如何穿过非常小的孔。这项研究的意义在于，它将提供扩大 DNA 作为生物材料的用途和开发基于分子连接的其他材料所需的信息。这项工作的更广泛影响包括培训不同的学生群体并开展研究。实验表明将扩展到其他领域，包括二维材料的研究，例如石墨烯，动质体可以作为有用的模型系统，使石墨烯技术更接近公众使用，以及寄生虫学，动质体的研究可以让研究人员更好地了解阻止寄生虫繁殖周期的方法。技术摘要：除了携带遗传信息的作用外，DNA还被探索作为可再生和可降解聚合物材料的基础，作为涂层的一部分以提高生物相容性DNA 的生物材料用途需要在分子水平上了解其物理特性。动质体是线粒体中发现的复杂 DNA 结构。锥虫寄生虫；每个动质体由数千个环状 DNA 分子组成，这些分子在类似于中世纪链甲的二维网络中拓扑连接。 DNA 作为生物材料的作用，并深入了解拓扑复杂的合成分子的物理学，研究人员将通过测量回转半径等参数来研究溶剂化学对动质体平衡构象的影响，回转半径是由竞争效应决定的。光镊将用于拉伸动体，测量其力响应和弹性​​模量，并量化索烷（连接环）非共价键的强度。纳米孔传感将用于测量动质体和较小的链状 DNA 结构在极端变形下的响应，这对于确定生物聚合物加工应用的适当条件至关重要。限制性酶对动质体的降解将用于调整其机械性能，确定其机械性能。网络拓扑，并更好地了解锥虫如何创建这些复杂的结构。作为更广泛的影响，将启动笔友计划，将代表性不足的群体的年轻人与学生研究人员联系起来。该奖项反映了这一点。通过使用基金会的智力价值和更广泛的影响审查标准进行评估，NSF 的法定使命被认为值得支持。

项目成果

Nanopore translocation of topologically linked DNA catenanes

拓扑连接的 DNA 索链的纳米孔易位

• DOI: 10.1103/physreve.107.024504
• 发表时间: 2023-02
• 期刊: Physical Review E
• 影响因子: 2.4
• 作者: Rheaume, Sierra N.;Klotz, Alexander R.
• 通讯作者: Klotz, Alexander R.

Percolation and dissolution of Borromean networks

博罗梅安网络的渗透和溶解

• DOI: 10.1103/physreve.107.024304
• 发表时间: 2023-02
• 期刊: Physical Review E
• 影响因子: 2.4
• 作者: Ferschweiler, Donald G.;Blair, Ryan;Klotz, Alexander R.
• 通讯作者: Klotz, Alexander R.