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1. Cooperative control of a DNA origami force sensor

   https://doi.org/10.1038/s41598-024-53841-3  

   Robbins, Ariel; Hildebolt, Hazen; Neuhoff, Michael; Beshay, Peter; Winter, Jessica O; Castro, Carlos E; Bundschuh, Ralf; Poirier, Michael G (December 2024, Scientific Reports)

   Abstract Biomolecular systems are dependent on a complex interplay of forces. Modern force spectroscopy techniques provide means of interrogating these forces, but they are not optimized for studies in constrained environments as they require attachment to micron-scale probes such as beads or cantilevers. Nanomechanical devices are a promising alternative, but this requires versatile designs that can be tuned to respond to a wide range of forces. We investigate the properties of a nanoscale force sensitive DNA origami device which is highly customizable in geometry, functionalization, and mechanical properties. The device, referred to as the NanoDyn, has a binary (open or closed) response to an applied force by undergoing a reversible structural transition. The transition force is tuned with minor alterations of 1 to 3 DNA oligonucleotides and spans tens of picoNewtons (pN). The DNA oligonucleotide design parameters also strongly influence the efficiency of resetting the initial state, with higher stability devices (≳10 pN) resetting more reliably during repeated force-loading cycles. Finally, we show the opening force is tunable in real time by adding a single DNA oligonucleotide. These results establish the potential of the NanoDyn as a versatile force sensor and provide fundamental insights into how design parameters modulate mechanical and dynamic properties. 

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2. Dissection of nanoconfinement and proximity effects on the binding events in DNA origami nanocavity

   https://doi.org/10.1093/nar/gkab1298  

   Jonchhe, Sagun; Pandey, Shankar; Beneze, Christian; Emura, Tomoko; Sugiyama, Hiroshi; Endo, Masayuki; Mao, Hanbin (January 2022, Nucleic Acids Research)

   Abstract Both ligand binding and nanocavity can increase the stability of a biomolecular structure. Using mechanical unfolding in optical tweezers, here we found that a DNA origami nanobowl drastically increased the stability of a human telomeric G-quadruplex bound with a pyridostatin (PDS) ligand. Such a stability change is equivalent to >4 orders of magnitude increase (upper limit) in binding affinity (Kd: 490 nM → 10 pM (lower limit)). Since confined space can assist the binding through a proximity effect between the ligand-receptor pair and a nanoconfinement effect that is mediated by water molecules, we named such a binding as mechanochemical binding. After minimizing the proximity effect by using PDS that can enter or leave the DNA nanobowl freely, we attributed the increased affinity to the nanoconfinement effect (22%) and the proximity effect (78%). This represents the first quantification to dissect the effects of proximity and nanoconfinement on binding events in nanocavities. We anticipate these DNA nanoassemblies can deliver both chemical (i.e. ligand) and mechanical (i.e. nanocavity) milieus to facilitate robust mechanochemical binding in various biological systems. 

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3. Recent Advances in Self-Assembled DNA Nanostructures for Bioimaging

   https://doi.org/10.1021/acsabm.2c00128  

   Yang, Qi; Chang, Xu; Lee, Jung Yeon; Olivera, Tiffany R.; Saji, Minu; Wisniewski, Henry; Kim, Suchan; Zhang, Fei (October 2022, ACS Applied Bio Materials)

   DNA nanotechnology has been proven to be a powerful platform to assist the development of imaging probes for biomedical research. The attractive features of DNA nanostructures, such as nanometer precision, controllable size, programmable functions, and biocompatibility, have enabled researchers to design and customize DNA nanoprobes for bioimaging applications. However, DNA probes with low molecular weights (e.g., 10–100 nt) generally suffer from low stability in physiological buffer environments. To improve the stability of DNA nanoprobes in such environments, DNA nanostructures can be designed with relatively larger sizes and defined shapes. In addition, the established modification methods for DNA nanostructures are also essential in enhancing their properties and performances in a physiological environment. In this review, we begin with a brief recap of the development of DNA nanostructures including DNA tiles, DNA origami, and multifunctional DNA nanostructures with modifications. Then we highlight the recent advances of DNA nanostructures for bioimaging, emphasizing the latest developments in probe modifications and DNA-PAINT imaging. Multiple imaging modules for intracellular biomolecular imaging and cell membrane biomarkers recognition are also summarized. In the end, we discuss the advantages and challenges of applying DNA nanostructures in bioimaging research and speculate on its future developments. 

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4. Mechanical Flexibility of DNA: A Quintessential Tool for DNA Nanotechnology

   https://doi.org/10.3390/s20247019  

   Saran, Runjhun; Wang, Yong; Li, Isaac T. (December 2020, Sensors)

   null (Ed.)

   The mechanical properties of DNA have enabled it to be a structural and sensory element in many nanotechnology applications. While specific base-pairing interactions and secondary structure formation have been the most widely utilized mechanism in designing DNA nanodevices and biosensors, the intrinsic mechanical rigidity and flexibility are often overlooked. In this article, we will discuss the biochemical and biophysical origin of double-stranded DNA rigidity and how environmental and intrinsic factors such as salt, temperature, sequence, and small molecules influence it. We will then take a critical look at three areas of applications of DNA bending rigidity. First, we will discuss how DNA’s bending rigidity has been utilized to create molecular springs that regulate the activities of biomolecules and cellular processes. Second, we will discuss how the nanomechanical response induced by DNA rigidity has been used to create conformational changes as sensors for molecular force, pH, metal ions, small molecules, and protein interactions. Lastly, we will discuss how DNA’s rigidity enabled its application in creating DNA-based nanostructures from DNA origami to nanomachines. 

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5. A Review on Origami Simulations: From Kinematics, To Mechanics, Toward Multiphysics

   https://doi.org/10.1115/1.4055031  

   Zhu, Yi; Schenk, Mark; Filipov, Evgueni T. (May 2022, Applied Mechanics Reviews)

   Abstract Origami-inspired systems are attractive for creating structures and devices with tunable properties, multiple functionalities, high-ratio packaging capabilities, easy fabrication, and many other advantageous properties. Over the past decades, the community has developed a variety of simulation techniques to analyze the kinematic motions, mechanical properties, and multiphysics characteristics of origami systems. These various simulation techniques are formulated with different assumptions and are often tailored to specific origami designs. Thus, it is valuable to systematically review the state-of-the-art in origami simulation techniques. This review presents the formulations of different origami simulations, discusses their strengths and weaknesses, and identifies the potential application scenarios of different simulation techniques. The material presented in this work aims to help origami researchers better appreciate the formulations and underlying assumptions within different origami simulation techniques, and thereby enable the selection and development of appropriate origami simulations. Finally, we look ahead at future challenges in the field of origami simulation. 

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