RUI: Materials Physics with 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.