Introduction to DNA origami 

DNA origami uses a long circular ssDNA as a template ('scaffold'), and hundreds of synthetic oligonucleotides ('staple') with programmed sequences to fold the scaffold into desired geometries. It has been attracted much attention since it has enabled programmed self-assembly of complex three-dimensional nanostructures. Typical DNA origami structures consist of a scaffold around 7249 to 8634 nucleotide (nt)-long, and up to 200 staple strands. Each staple strand has complementary sequences to its binding sites on the scaffold, therefore a unique staple set for each target structure should be constructed. Molecular self-assembly between DNA strands is initiated by the thermal annealing process with buffer containing multivalent cation such as magnesium chloride to neutralize the negative charge of DNA. 

Modular shape and stiffness design

The versatility of DNA origami in shape design to create almost any arbitrary geometry with nanometer-scale precision has been proved by a number of successful methods both with lattice-packed or lattice-free assembly rules, as well as algorithmic inverse design procedures based on them. In addition to the shape design, spatial controllability of mechanical stiffness of DNA origami opened a way to create dynamic and functional DNA nanostructures. Unlike other bulk nanomaterials, the availability of designing localized and site-directed flexible regions within a nanostructure is one of the major advantages of the DNA origami technology. By utilizing it, multiple applications were demonstrated such as single-molecule sensors, molecular substrates and carriers, plasmonic structures and nanomechanical devices. However, due to the lack of proper design motifs that effectively control the local mechanical stiffness without altering the geometric features or deteriorating the structural integrity, methods for controlling the mechanical stiffness of DNA nanostructures have rarely been advanced. 

             In order to provide an effective stiffness control design method while minimizing the cost of staple replacement, we developed a module-based stiffness design approach in DNA origami. It should be noted that in order to control the mechanical stiffness of DNA origami structures with high staple reusability, the most important design principle is the conservation of the initially designed scaffold route. In our method, modification of the local structural stiffness is only mediated by revising the sequence of staple strands therein. Also, we utilized the computational prediction platform to validate the result of design modification prior to the experiment, which enables the significant reduction of time and cost during the design process.

Computational approaches

The demand for a robust design validation tool has been increased since the complexity and diversity of shapes and functions of DNA origami structures have been increased. A mechanical model based on finite element analysis (FEA) was developed by Kim et al. (Nucleic Acids Res., 2009), to predict the 3D shape and flexibility of DNA nanostructures within a few minutes. This approach is particularly useful when a DNA origami structure contains the regions with large deformations induced by mechanical perturbations, since it takes a very long simulation time in conventional methods and difficult to predict their effect experimentally as well. In case of investigating more detailed information of DNA nanostructures, all-atom molecular dynamics (MD) simulation or coarse-grained simulations are used. 

*Collaborators: Jae Young Lee (MD), Young-Joo Kim (FEA) 

I learned the MEMS fabrication techniques during the research student program in Inter-university Semiconductor Research Center (ISRC) at SNU. By utilizing the conventional photolithography process, holes or grooves with different geometries can be engraved on the silicon wafer. Such patterns can be easily replicated using thermo- or photo-curable polymer materials. Additional process such as polymer deposition or UVO etching can modulate the wetting property of surfaces. Also, sputtering of platinum layer onto the polymer structure can be utilized as mechanical sensor or electric connector application.