"Functionalized DNA Nanostructures for Membrane Engineering" by Qiancheng Xiong

Date of Award

Fall 2023

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Cell Biology

First Advisor

Lin, Chenxiang

Abstract

DNA nanotechnology is a powerful tool for constructing precisely designed nanostructures with applications in diverse fields, including synthetic biology, nanomedicine, and biomolecular engineering. This dissertation explores the use of DNA nanotechnology in membrane engineering, focusing on developing DNA endoskeleton-supported membranes and large functionalized DNA-toxin nanopores. The first approach encountered challenges while constructing interlocked DNA nanostructures for endoskeleton-supported membranes. The negative results highlighted the need to optimize the interlocked DNA endoskeleton cage design further to ensure its practical application in templating fully exposed, continuous membranes. The second approach incorporated pneumolysins into DNA-origami channels to create large, functionalized DNA-toxin nanopores. These hybrid pores spontaneously formed in cholesterol-rich membranes, with lumen widths exceeding 20 nm. The DNA-origami channel facilitated uniform pore size and allowed the integration of additional diffusion-restricting molecules as size-selective gatekeepers for controlling macromolecule flux in and out of synthetic membrane compartments. These findings contribute to the ongoing development of membrane engineering, which holds promise for advancing research in membrane biology, synthetic biology, and nanomedicine, and expand DNA nanotechnology's design space and possible applications.

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