(9c) Programming Biomaterial Self-Assembly to Advance Molecular Robotics and Gene Delivery

Synthesizing biomaterials using nature’s building blocks enables engineers to construct highly programmable devices with unprecedented control over chemical and physical properties, providing a basis for next generation smart materials with applications in biology, manufacturing, and medicine. Here, I will highlight my advances using engineered biomaterials to build 1) controllable nanoscale kinematic joints and mechanisms and 2) charge-driven polymer assemblies for nucleic acid delivery. First, we leveraged the unique structural properties of DNA to create mechanical joints and multi-joint mechanisms with defined 2D and 3D motion. We then use these to demonstrate multiple actuation methods for conformational control of dynamic nanostructures. Second, we took advantage of the strong negative charge of therapeutic nucleic acids to sequester them inside a nanoparticle core using cationic polypeptides, while a neutral polymer shell protects them from nucleases and immune response. We probed the molecular details of each component to establish structure-property relationships and to understand their effect on the stability of the nanoparticles, improving efficient design and construction capabilities for therapeutic delivery devices. I plan to use this groundwork to advance the construction of complex engineering devices in the future, incorporating aspects from both assembly methods in a largely unexplored fashion to translate molecular interactions to larger-scale biohybrid materials.