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.

非技术摘要：DNA以其在携带遗传信息中的作用而闻名，但是DNA分子也可以用作可再生和可生物降解的材料，以及改善人体与合成成分（如假体不症状）之间界面的工具。使DNA用作生物材料需要了解其在分子水平上的物理特性。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：锥虫家族的寄生虫，导致诸如睡眠疾病和利什曼病等疾病的疾病具有复杂的DNA结构，称为动力体。动力体是一个连接的网络，该网络像中世纪的链式装甲一样连接连接的数千个小圆形DNA分子。具有这种复杂连接结构的材料在自然界中没有发现，并且很难人为地生产，因此这种类型的材料的特性不太了解。研究人员试图通过研究动力学，了解其材料特性并研究锥虫细胞如何产生它们，以提高对DNA生物材料的了解。他们提出的实验包括研究化学条件如何改变动力学成形体的大小，拉伸动力学成形素以测量其材料的强度和韧性，将动力学成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很小的小孔。所有这些方面都与生物材料设计过程有关。这项研究的意义在于，它将提供扩大DNA用作生物材料的使用所需的信息，并基于分子链接开发其他材料。这项工作的更广泛影响涉及培训一群学生组和进行实验，这些实验将扩展到其他领域，包括研究二维材料（例如石墨烯）的研究，这些材料（例如石墨烯）可能会成为一种有用的模型系统，以使石墨烯技术更接近公众使用，并可以更好地了解研究人员的研究，从而使研究人员了解范围的研究。摘要：除了其在携带遗传信息中的作用外，DNA还被探索为可再生和可降解的聚合物材料的基础，作为提高涂料的涂料的一部分，以改善焦缘的生物相容性，并作为药物递送的底物。 DNA的生物材料用途需要了解其在分子水平上的物理特性。分子的拓扑对其材料特性具有显着影响。动力学是在锥虫寄生虫线粒体中发现的复杂DNA结构。每个动力学成形术由成千上万的圆形DNA分子拓扑结合，这些循环链接在类似于中世纪链式甲甲的二维网络中。这项工作着重于动作成形体的材料特性，这是对DNA作为生物材料作用的广泛研究的一部分，并洞悉拓扑复杂的合成分子的物理学。研究人员将通过测量参数（例如回旋半径）来研究偿付能力化学对动作成形体等效构象的影响，该参数取决于弯曲刚度和热波动的竞争作用。光学镊子将用于伸展动力学，测量其力响应和弹性模量，并量化Catenane（链接环）非共价键的强度。纳米孔灵敏度将用于测量极端变形下的动力学成体和较小的枢纽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。通过限制酶降解动力学成体将用于调整其机械性能，确定其网络拓扑，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，将启动一项Pen PAL计划，以将代表性不足小组的青年与学生研究人员联系起来。该奖项反映了NSF的法定任务，并使用基金会的知识分子优点和更广泛的影响评估标准，被认为是通过评估来获得的支持。