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The ability to self‐assemble DNA nanodevices with programmed structural dynamics that can sense and respond to the local environment can enable transformative applications in fields including mechanobiology and nanomedicine. The responsive function of biomolecules is often driven by alterations in conformational distributions mediated by highly sensitive interactions with the local environment. In this review, the current state‐of‐the‐art in constructing complex DNA geometries with dynamic and mechanical properties to enable a molecular scale force measurement is first summarized. Next, an overview of engineering modular DNA devices that interact with cell surfaces is highlighted detailing examples of mechanosensitive proteins and the force‐induced dynamic molecular interaction on the downstream biochemical signaling. Finally, the challenges and an outlook on this promising class of DNA devices acting as nanomachines to operate at a low piconewton range suitable for a majority of biological effects or as hybrid materials to achieve higher tension exertion required for other biological investigations, are discussed. [ABSTRACT FROM AUTHOR]

Nucleic acids (DNA and RNA) are widely used to construct nanoscale structures with ever increasing complexity1–14 for possible applications in fields as diverse as structural biology, biophysics, synthetic biology and photonics. The nanostructures are formed through one-pot self-assembly, with early examples typically containing on the order of 10 unique DNA strands. The introduction of DNA origami4, which uses many staple strands to fold one long scaffold strand into a desired structure, gave access to kilo- to mega-dalton nanostructures containing about 102 unique DNA strands6,7,10,13 . Aiming for even larger DNA origami structures is in principle possible15,16, but faces the challenge of having to manufacture and route an increasingly long scaffold strand. An alternative and in principle more readily scalable approach uses DNA brick assembly8,9, which doesn’t need a scaffold and instead uses hundreds of short DNA brick strands that self-assemble according to specific inter-brick interactions. First-generation bricks used to create 3D structures are 32-nt long with four 8-nt binding domains that directed 102 distinct bricks into well-formed assemblies, but attempts to create larger structures encountered practical challenges and had limited success.9 Here we show that a new generation of DNA bricks with longer binding domains makes it possible to self-assemble 0.1 – 1 giga-dalton three-dimensional nanostructures from 104 unique components, including a 0.5 giga-dalton cuboid containing 30,000 unique bricks and a 1 giga-dalton rotationally symmetric tetramer. We also assemble a cuboid containing 10,000 bricks and 20,000 uniquely addressable ‘nano-voxels’ that serves as a molecular canvas for three-dimensional sculpting, with introduction of sophisticated user-prescribed 3D cavities yielding structures such as letters, a complex helicoid and a teddy bear. We anticipate that, with further optimization, even larger assemblies might be accessible and prove useful as scaffolds or for positioning functional components.

The creation of nanometre-sized structures that exhibit controllable motions and functions is a critical step towards building nanomachines. Recent developments in the field of DNA nanotechnology have begun to address these goals, demonstrating complex static or dynamic nanostructures made of DNA. Here we have designed and constructed a rhombus-shaped DNA origami ‘nanoactuator' that uses mechanical linkages to copy distance changes induced on one half (‘the driver') to be propagated to the other half (‘the mirror'). By combining this nanoactuator with split enhanced green fluorescent protein (eGFP), we have constructed a DNA–protein hybrid nanostructure that demonstrates tunable fluorescent behaviours via long-range allosteric regulation. In addition, the nanoactuator can be used as a sensor that responds to specific stimuli, including changes in buffer composition and the presence of restriction enzymes or specific nucleic acids.

Thirty percent of the human proteome is composed of membrane proteins that can perform a wide range of cellular functions and communications. They represent the core of modern medicine as the targets of about 50 % of all prescription pharmaceuticals. However, elucidating the structure of membrane proteins has represented a constant challenge, even in the modern era. To date, only a few hundred high-resolution structural models of membrane proteins are available. This chapter describes the emergence of DNA nanotechnology as a powerful tool for the structural characterization of membrane protein using solution-state nuclear magnetic resonance (NMR) spectroscopy. Here, we detail the large-scale synthesis of detergent-resistant DNA nanotubes that can be assembled into a dilute liquid crystal to be used as a weak-alignment media in solution NMR structure determination of membrane proteins.