2024 Theses Doctoral

Programming lattice organizations through engineering isotropic and anisotropic DNA bonds

Minevich, Brian

Over recent decades, DNA-based methods for programmable self-assembly has tremendous progress in the design, synthesis, and three-dimensional (3D) organization of functional nanomaterials for practical applications. This dissertation will demonstrate how DNA binding interactions can be leveraged for the fabrication of complex nanoscale architectures through the use of isotropic and anisotropic DNA binding interactions.

In Chapter 1, I will review recent progress in the field of DNA-based self-assembly strategies. Then, in Chapter 2, I will discuss our work that involves the use of DNA as a means of regulating the isotropic interactions of spherical nanoparticle shells to facilitate the programmable assembly of high- and low-coordinated 3D structures.

Chapters 3-4 will demonstrate the “material voxels” self-assembly strategy where firstly, the valency and geometry of the nanoscale frames determine the crystallographic symmetry of the resultant assembled superlattice, and secondly, the use of addressable binding specificity can be utilized as a part of an inverse design strategy to both determine the number of unique voxels and binding motifs and assemble complex 3D architectures. This strategy was then used to design and fabricate a Distributed Bragg reflector (DBR) with enhanced tunability compared to traditional DBRs.

Later, in Chapter 5, I designed DNA bonds with addressable binding specificity, in this case, using a series of orthogonal DNA strand displacement reactions to control the activity of the DNA bonds prescribed at the vertices of the DNA origami voxels. I also share work, in Chapter 6, that shows an additional parameter related to the addressability of the DNA bonds, the relative energies of the programmable sequences, to manipulate the morphology of the self-assembled domains.

In addition to the organization of metallic particles via the material voxels assembly strategy, Chapter 7 reveals how DNA bonds can be used to organize functional proteins into ordered 2D and 3D organizations, while also retaining the biological activity of the captured proteins, in this case ferritin. In Chapter 8 I will describe how our DNA-based materials can be used to test the effectiveness of radioprotective agents to mitigate against DNA damage from sources of ionizing radiation. In Chapter 9, I will outline additional work that I have done, both published and ongoing, that are related to the DNA-based self-assembly strategies outlined in this thesis overall. Then lastly, in Chapter 10, I will discuss the conclusions we can draw from this dissertation overall, and detail further efforts that can use this research as foundational work.