Abstract
Curved structures found in both artificial constructions and natural biomolecular assemblies enable the gain of sophisticated properties and adaptability. They provide a source of inspiration for the DNA de novo design of innovative biomimetic architectures, materials, and devices with enhanced functionalities. However, the DNA nanotechnology field encounters challenges in achieving complex curved structures in 3D space. While already existing methodologies enable the design and production of DNA origami with curvatures, the inherent constraints imposed by the DNA geometry pose significant limitations in achieving high yields of well-defined structures with precise curvatures and complexities. In response to these challenges, this thesis presents a general method to fold arbitrary 3D curved structures using a routing algorithm that traces scaffold strands along curved surfaces. Crossover positioning is made by the user using the 3D view panel, directly from the intended geometry of the desired shape. This new method has been implemented in the design software ENSnano which offers a highly automated workflow for designing complex curved DNA nanostructures. In this work, over ten origami structures with unprecedentedly complex curvatures defined in 3D space were designed. The accuracy of the programmed and folded objects has been validated through electron microscopy. This work also presents how we can fold DNA nanostructures in physiologically relevant conditions, notably by using these new methods of design. Hence, we describe the accurate folding of three-dimensional DNA nanostructures at 37°C with concentrations of salt relevant to physiological conditions. Hence, we believe that the sleek and user-friendly geometric interface of ENSnano will catalyze the design of biomimetic nanostructures with the potential to expand the range of achievable shapes in DNA nanotechnology and applications in the biomedical field.