Biophysical Modeling of Nucleic Acid Nanostructure Solution Shape and Stability

Abstract

Programmed self-assembly of RNA and DNA provides a powerful approach to designing active, functional nanometer-scale structures for biomolecular science and technology. Scaffolded DNA Origami employs a long single-stranded DNA template to guide the hybridization of hundreds of shorter oligonucleotide staple strands to form twisted and bent double-stranded DNA structures of high precision and yield with well-defined mechanical properties. Biophysical models of nanostructure formation and stability are needed to inform the DNA Origami design process, which currently proceeds largely based on physical intuition and trial-and-error. Here we present a physics-based model for DNA Origami that incorporates double-stranded DNA mechanical properties in addition to screened electrostatic interactions on 3D solution shape and flexibility. Results are presented in detail for an eight-layer DNA Origami block designed on a square lattice (Ke et al., JACS 2009), whose 3D solution shape is computed under experimental folding conditions, revealing an undulating pattern of individual DNA double helices due to interhelix electrostatic repulsion. Effects of crossover spacing on solution shape and mechanical properties are also discussed.