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Tailoring the Mechanical Stiffness of DNA Nanostructures Using Engineered Defects.

As scaffolded DNA origami enables the construction of diverse DNA nanostructures with predefined shapes, precise modulation of their mechanical stiffness remains challenging. We demonstrate a modular design method to widely and precisely control the mechanical flexibility of scaffolded DNA origami nanostructures while maintaining their overall structural integrity and geometric characteristics. Individually engineered defects that are short single-stranded DNA (ssDNA) gaps could reduce up to 70% of the bending stiffness of DNA origami constructs with different cross-sectional shapes. We further developed a computational analysis platform predicting the bending stiffness of a defect-engineered DNA nanostructure quickly during the design process, to offer an efficient way of designing various DNA constructs with required mechanical stiffness in a desired shape for a targeted function.