RUI: Materials Physics with Kinetoplast DNA

非技术综述：DNA最为人所知的是它在携带遗传信息方面的作用，但DNA分子也可以用作可再生和可生物降解的材料，以及改善人体与假体等合成部件之间接口的工具。将DNA用作生物材料需要在分子水平上了解其物理性质。自然界产生的DNA具有复杂的结构，超出了我们细胞中的螺旋：锥虫家族的寄生虫拥有一种复杂的DNA结构，称为动泡体。锥虫家族的寄生虫会导致睡眠病和利什曼病等疾病。动粒是由数以千计的环状小DNA分子连接而成的网络，就像中世纪的链甲一样。具有这种复杂连接结构的材料在自然界的其他地方是找不到的，很难人工生产，所以这种类型的材料的性质还没有被很好地了解。研究人员试图通过研究动生质体，了解它们的材料特性，并研究锥体细胞是如何产生它们的，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粒大小，拉伸动粒以测量它们的材料强度和韧性，将动粒与不是由连接的环组成的材料进行比较，以及探索连接的分子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有关。这项研究的意义在于，它将为扩大DNA作为生物材料的使用以及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包括培训不同的学生群体，并进行将延伸到其他领域的实验，包括研究二维材料，如石墨烯，对于这些材料，动殖体可以作为有用的模型系统，使石墨烯技术更接近公共使用，以及寄生虫学，对动殖体的研究可能使研究人员更好地了解防止寄生虫繁殖周期的方法。技术摘要：除了在携带遗传信息方面的作用外，DNA还被探索为可再生和可降解聚合物材料的基础，作为涂层的一部分，以提高植入物的生物相容性，以及作为药物输送的基质。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很大的影响。动质体是在锥虫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，在拓扑上连接在一个类似于中世纪链甲的二维网络中。这项工作的重点是动丝泡体的材料特性，作为DNA作为生物材料作用的更广泛研究的一部分，并提供对拓扑复杂的合成分子的物理学的洞察。研究人员将通过测量旋转半径等参数来研究溶剂化学对动丝泡体平衡构象的影响，旋转半径是由弯曲刚性和热波动的竞争效应决定的。光钳将被用来拉伸动质外体，测量它们的力响应和弹性模数，并量化连环(连接环)非共价键的强度。纳米孔传感将用于测量动泡体和较小的链状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。通过限制性内切酶降解动泡体将被用来调整它们的机械性能，确定它们的网络拓扑，并更好地了解锥虫是如何创建这些复杂结构的。作为更广泛的影响，将启动笔友计划，将来自代表性不足群体的年轻人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。

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.