权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

RUI: Materials Physics with Kinetoplast DNA

RUI：利用 Kinetoplast DNA 进行材料物理

基本信息

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

项目摘要

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.

非技术总结：DNA以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，以及改善人体与人工合成组件（如假体植入物）之间界面的工具。使DNA作为生物材料的使用需要在分子水平上了解其物理特性。自然界产生的DNA具有复杂的结构，超出了我们细胞中发现的螺旋：锥虫家族的寄生虫，导致睡眠病和利什曼病等疾病，具有称为动基体的复杂DNA结构。动基体是由成千上万的环状DNA分子组成的网络，它们像中世纪的锁子甲一样连接在一起。具有这种复杂连接结构的材料在自然界其他地方找不到，也很难人工生产，因此这类材料的性质还不太清楚。研究人员试图通过研究动质体，了解它们的材料特性，并研究锥虫细胞如何产生它们来促进对DNA生物材料的理解。他们提出的实验包括研究化学条件如何改变动质体的大小，拉伸动质体以测量其材料强度和韧性，将动质体与非连接环制成的材料进行比较，并探索连接分子的系统如何通过非常小的孔。所有这些方面都与生物材料设计过程相关。这项研究的重要性在于，它将为扩大DNA作为生物材料的用途和开发基于分子连接的其他材料提供所需的信息。这项工作的更广泛的影响涉及培训不同的学生群体，并进行将扩展到其他领域的实验，包括石墨烯等二维材料的研究，其中动质体可以作为一个有用的模型系统，使石墨烯技术更接近公众使用，以及寄生虫学，对动质体的研究可以让研究人员更好地了解阻止寄生虫生殖周期的方法。技术摘要：除了其在携带遗传信息中的作用外，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改善植入物的生物相容性，以及作为药物递送的基质。DNA的生物材料用途需要在分子水平上了解其物理性质。分子的拓扑结构对其材料性质有重要影响。动质体是在锥虫寄生虫的线粒体中发现的复杂DNA结构;每个动质体由数千个环状DNA分子组成，这些分子在拓扑学上连接在一个类似于中世纪锁子甲的二维网络中。这项工作的重点是作为DNA作为生物材料的作用更广泛的调查的一部分，动质体的材料特性，并提供深入了解拓扑复杂的合成分子的物理。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，回转半径由弯曲刚度和热波动的竞争效应决定。光镊将用于拉伸动质体，测量它们的力响应和弹性模量，并量化链烷（连接环）非共价键的强度。纳米孔传感将用于测量极端变形下动质体和较小链状DNA结构的响应，这对于确定生物聚合物加工应用的适当条件至关重要。限制酶降解动质体将用于调整其机械性能，确定其网络拓扑结构，并更好地了解锥虫如何创建这些复杂的结构。作为一个更广泛的影响，将启动一个Pen奖计划，将代表性不足的群体的青年与学生研究人员联系起来。该奖项反映了NSF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。