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Abstract The intrinsic complexity of many mesoscale (10–100 nm) cellular machineries makes it challenging to elucidate their topological arrangement and transition dynamics. Here, we exploit DNA origami nanospring as a model system to demonstrate that tens of piconewton linear force can modulate higher-order conformation dynamics of mesoscale molecular assemblies. By switching between two chemical structures (i.e., duplex and tetraplex DNA) in the junctions of adjacent origami modules, the corresponding stretching or compressing chemo-mechanical stress reversibly flips the backbone orientations of the DNA nanosprings. Both coarse-grained molecular dynamics simulations and atomic force microscopy measurements reveal that such a backbone conformational switch does not alter the right-handed chirality of the nanospring helix. This result suggests that mesoscale helical handedness may be governed by the torque, rather than the achiral orientation, of nanospring backbones. It offers a topology-based caging/uncaging concept to present chemicals in response to environmental cues in solution. 

Invention of DNA origami has transformed the fabrication and application of biological nanomaterials. In this review, we discuss DNA origami nanoassemblies according to their four fundamental mechanical properties in response to external forces: elasticity, pliability, plasticity and stability. While elasticity and pliability refer to reversible changes in structures and associated properties, plasticity shows irreversible variation in topologies. The irreversible property is also inherent in the disintegration of DNA nanoassemblies, which is manifested by its mechanical stability. Disparate DNA origami devices in the past decade have exploited the mechanical regimes of pliability, elasticity, and plasticity, among which plasticity has shown its dominating potential in biomechanical and physiochemical applications. On the other hand, the mechanical stability of the DNA origami has been used to understand the mechanics of the assembly and disassembly of DNA nano-devices. At the end of this review, we discuss the challenges and future development of DNA origami nanoassemblies, again, from these fundamental mechanical perspectives. 

Mechanical unfolding of biomolecular structures has been exclusively performed at the single-molecule level by single-molecule force spectroscopy (SMFS) techniques. Here we transformed sophisticated mechanical investigations on individual molecules into a simple platform suitable for molecular ensembles. By using shear flow inside a homogenizer tip, DNA secondary structures such as i-motifs are unfolded by shear force up to 50 pN at a 77 796 s −1 shear rate. We found that the larger the molecules, the higher the exerted shear forces. This shear force approach revealed affinity between ligands and i-motif structures. It also demonstrated a mechano-click reaction in which a Cu( i ) catalyzed azide–alkyne cycloaddition was modulated by shear force. We anticipate that this ensemble force spectroscopy method can investigate intra- and inter-molecular interactions with the throughput, accuracy, and robustness unparalleled to those of SMFS methods. 

By incorporating pH responsive i-motif elements, we have constructed DNA origami nanosprings that respond to pH changes in the environment. Using an innovative force jump approach in optical tweezers, we have directly measured the spring constants and dynamic recoiling responses of the DNA nanosprings under different forces. These DNA nanosprings exhibited 3 times slower recoiling rates compared to duplex DNA backbones. In addition, we observed two distinct force regions which show different spring constants. In the entropic region below 2 pN, a spring constant of ∼0.03 pN nm −1 was obtained, whereas in the enthalpic region above 2 pN, the nanospring was 17 times stronger (0.5 pN nm −1 ). The force jump gave a more accurate measurement on nanospring constants compared to regular force ramping approaches, which only yielded an average spring constant in a specific force range. Compared to the reported DNA origami nanosprings with a completely different design, our nanospring is up to 50 times stiffer. The drastic increase in the spring constant and the pH responsive feature allow more robust applications of these nanosprings in many mechanobiological processes.