Shih, WilliamSubramaniam, Rahul Vignesh2026-01-1320232025-05-282023Subramaniam, Rahul Vignesh. 2023. Mimicking the Structure and Polymerization Behavior of Clathrin Using DNA Origami. Bachelors Thesis, Harvard University Engineering and Applied Sciences.30315511https://dash.harvard.edu/handle/1/42725004DNA origami is a recently developed nanotechnology paradigm that has demonstrated significant convenience and utility for its ability to self-assemble nanostructures with exquisite control over shape and behavior. Controlling the polymerization and self-assembly properties of DNA origami monomers and polymers would allow for the triggered assembly of large-scale structures with applications in diagnostics and nanofabrication. To that end, we developed a DNA origami system that mimics the structure and polymerization activity of the cellular protein clathrin, which is known for its finely tuned nucleation behavior based on interactions between non-nearest neighbor monomers. We designed triskelion-shaped DNA origami monomers that folded into clathrin-shaped structures with polymerization functionality and multiple distinct binding domains that could engage in non-nearest neighbor interactions. We experimentally verified multi-domain monomer folding using agarose gel electrophoresis and transmission electron microscopy. Guided by a set of abstract models and physical intuitions that incorporated principles from thermodynamics and graph theory, we then designed polymers to recreate the hexagonal lattices formed by clathrin, and progressively improved lattice formation using an iterative process. Hexagonal clathrin-like polymer lattices were successfully formed using a set of 14 rationally designed and unique monomers. This research lays key groundwork for expanding the control that can be exerted over nanoscale self-assembly and nucleation behavior in a biologically inspired fashion.application/pdfenBiomedical engineeringPhysicsThesis or Dissertation2026-01-13