Biological cells can adapt, replicate, and repair in ways that are unmatched by man-made devices. At the core of these complex behaviors are many dynamic processes that are difficult to deconstruct, and lack the modularity of electrical and mechanical systems. For example, shape adaptation in cells arises from the interplay of receptors, gene networks, and self-assembling cytoskeletal scaffolds. While the interplay of elements performing sensing, control, and actuation is apparent, it is not clear how to program similar behaviors in biological or synthetic matter using a minimal number of components and reactions. To address this general challenge, we follow a reductionist approach and we combine a systems-engineering theoretical analysis with experiments on nucleic acid systems. Nucleic acids are versatile molecules whose interactions and kinetic behaviors can be rationally designed from their sequence content; further, they are relevant in a number of native and engineered cellular pathways, as well as in biomedical and nanotechnology applications. I will illustrate our approach using as an example the design and synthesis of self – assembling DNA and RNA nanotubes that can be programmed to respond to environmental inputs and to canonical molecular signal generators such as pulse generators and oscillators. I will
stress how mathematical modeling and control theory are essential to help identify design principles, to guide experiments, and to explain observed phenomena.