DNA Nanotechnolgy Enabled Molecular Mechanisms and Applications

DNA is well known for its function as a genetic information carrier. Based on its base pairing property, DNA can retain and reproduce the information. In recent decades, the base complementarity has been explored beyond its original function and takes DNA engineering to a new stage. With the recognition of specific bases in a DNA sequence, programmability and accessibility can be achieved for a DNA-made nanostructure. In addition, numerous reactive chemical groups may be linked to DNA strands which makes DNA nanotechnology more important. With these unique strength, DNA nanotechnology can serve as a powerful tool for molecular biology research including nanostructure construction and signal processing. DNA engineering can bring new characterization and control methods for various other scientific areas. In order to achieve better control of DNA, one must study the mechanisms and dynamics behind DNA nanotechnology.

This thesis investigates DNA nanotechnology, exploring the interactions of engineered DNA molecules with small molecules, proteins, nanoparticles, and cells. As a signal molecule, DNA is engineered in a logic gate for cargo pickup and release as well as in a dynamic walker device for controlled drug release for cancer cell treatment. In these DNA-based nanosystems, we develop novel logic gate mechanisms and study biomolecular reaction kinetics. In addition, DNA is also used to modulate surface gliding microtubules in vitro where individual microtubules are re-directed locally. With a fundamental understanding of DNA signaling systems, we propose to program activity of synthetic cells. Here, liposomes are constructed from phospholipids with transmembrane pores made of DNA origami. DNA signals are recognized and processed with transmembrane pores on synthetic cells. Programmable cell aggregation was demonstrated as a proof-of-principle. We envision that this thesis will provide a deeper understanding of DNA nanotechnology for both fundamental mechanisms and engineering applications. New powerful platforms for molecular and cellular biology systems could be developed and possibly help study dynamics and kinetics in physiology and medicine.