Young-Joo Kim

Atomic force microscopy (AFM) is one of the most popular imaging and characterizing methods applicable to a wide range of nanoscale material systems. However, high‐resolution imaging using AFM generally suffers from a low scanning yield due to its method of raster scanning. Here, a systematic method of data acquisition and preparation combined with a deep‐learning‐based image super‐resolution, enabling rapid AFM characterization with accuracy, is proposed. Its application to measuring the geometrical and mechanical properties of structured DNA assemblies reveals that around a tenfold reduction in AFM imaging time can be achieved without significant loss of accuracy. Through a transfer learning strategy, it can be efficiently customized for a specific target sample on demand.

Recent advances in DNA nanotechnology led the fabrication and utilization of various DNA assemblies, but the development of a method to control their global shapes and mechanical flexibilities with high efficiency and repeatability is one of the remaining challenges for the realization of the molecular machines with on-demand functionalities. DNA-binding molecules with intercalation and groove binding modes are known to induce the perturbation on the geometrical and mechanical characteristics of DNA at the strand level, which might be effective in structured DNA assemblies as well. Here, we demonstrate that the chemo-mechanical response of DNA strands with binding ligands can change the global shape and stiffness of DNA origami nanostructures, thereby enabling the systematic modulation of them by selecting a proper ligand and its concentration. Multiple DNA-binding drugs and fluorophores were applied to straight and curved DNA origami bundles, which demonstrated a fast, recoverable, and controllable alteration of the bending persistence length and the radius of curvature of DNA nanostructures. This chemo-mechanical modulation of DNA nanostructures would provide a powerful tool for reconfigurable and dynamic actuation of DNA machineries.

The ultrasensitive threshold response is ubiquitous in biochemical systems. In contrast, achieving ultrasensitivity in synthetic molecular structures in a controllable way is challenging. Here, we propose a chemomechanical approach inspired by Michell’s instability to realize it. A sudden reconfiguration of topologically constrained rings results when the torsional stress inside reaches a critical value. We use DNA origami to construct molecular rings and then DNA intercalators to induce torsional stress. Michell’s instability is achieved successfully when the critical concentration of intercalators is applied. Both the critical point and sensitivity of this ultrasensitive threshold reconfiguration can be controlled by rationally designing the cross-sectional shape and mechanical properties of DNA rings.

Structural DNA nanotechnology plays an ever-increasing role in advanced biomolecular applications. Here, we present a computational method to analyze structured DNA assemblies rapidly at near-atomic resolution. Both high computational efficiency and molecular-level accuracy are achieved by developing a multiscale analysis framework. The sequence-dependent relative geometry and mechanical properties of DNA motifs are characterized by the all-atom molecular dynamics simulation and incorporated into the structural finite element model successfully without significant loss of atomic information. The proposed method can predict the three-dimensional shape, equilibrium dynamic properties, and mechanical rigidities of monomeric to hierarchically assembled DNA structures at near-atomic resolution without adjusting any model parameters. The calculation takes less than only 15 min for most origami-scale DNA nanostructures consisting of 7000–8000 base-pairs. Hence, it is expected to be highly utilized in an iterative design–analysis–revision process for structured DNA assemblies.

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.