Dynamic synthetic Biological systems Programmed by DNA Designs

Deoxyribonucleic acid or DNA is an essential component in cells and organisms for genetic information storage and transduction. The base paring chemistry offers excellent programmability and structural predictability. This gives rise to the field of DNA nanotechnology, which uses DNA to design nanostructures and nanomachines with unprecedented designability and controllability. With the development of DNA nanotechnology, numerous chemical tools have been introduced for designing complex molecular mechanisms with DNA molecules. Various nanostructures of arbitrary shapes have been demonstrated, which shows the immense potential of DNA-based engineering. Dynamic nanodevices and their programmable actuations have also been successfully realized using DNA strand displacement and/or enzymatic reactions.

With controllable interactions with various biomolecules, it is possible to implement DNA in synthetic biological systems to program their behaviors. Two systems with programmed behaviors are introduced in this dissertation. The first system is a lipid-based protocell that can perform programmed migration with DNA-based mechanisms. This model system extracts chemical energy from fuel strands via enzymatic reaction and converts it into autonomous translocation on a surface. A mechanistic model is proposed to understand the migration dynamics. Furthermore, a path-tracking behavior between synthetic vesicles is demonstrated, which mimics cellular chemotaxis for the first time.

The second synthetic biological system explored is DNA origami structures capable of programmable auxetic reconfiguration. Auxetic materials are artificial systems with a negative Poisson’s ratio, which show great promise in various applications including space engineering and flexible/wearable electronics. With DNA-based sliding mechanisms, the proposed auxetic architecture can switch between two conformations with different Poisson’s ratios. The proposed strategy may be applied to designing adaptive materials or biochemical sensors with mechanical responses. The DNA-programmed behaviors demonstrated in this dissertation show unprecedented versatility and programmability, thus opening new opportunities for using molecular mechanisms to control synthetic biological systems with complex functions in diverse areas including biology, biomedicine, and material sciences.