Mechanical DNA Origami to Investigate Biological Systems

Abstract

ciently flexible to be packaged into nuclei around chromosomes and be subjected to various processes, such as replication and transcription, while also behaving as an entropic spring. [1,2] Today, DNA is increasingly being used as a building material to construct nano-objects with defined shape and size. The principle of Watson-Crick complementarity permits the design and production of self-assembling macromolecular objects with custom 3D shape. Of particular importance, these nanodevices can serve as molecular machines inspired by nature that can perform complex tasks dynamically and reliably using different design approaches. Creating these DNA nano-objects with specified shapes was first conceptualized more than 40 years ago by Seeman [3] and experimentally achieved 10 years later. [4] A significant breakthrough in the construction of nanometer-sized DNA objects occurred in 2006 with the introduction of the 2D DNA origami method by Rothemund, [5] and 3D DNA origami method introduced by Shih et al. in 2009. [6] Since these developments, DNA origami method has been thoroughly tested and applied to become, progressively, the gold standard method to build DNA nanostructures. [7] Self-assembled DNA origami are made from a scaffold strand of single-stranded DNA (ssDNA), typically M13 phage genomic DNA, which is folded by a complementary set of short oligonucleotide staple strands. [5,6,8] Initial DNA origami structures were static objects, albeit able to incorporate functionalized chemistries and biomolecules in a site-specific manner with well-defined spatial arrangement. [5,9,10] The well-characterized DNA-base pairing provides an easy means to control DNA interactions. This has allowed sequence programmability to rationalize the design into precisely defined geometries with increasingly complexity, including 2D, [11] 3D lattice, [12] and wireframe structures [13,14] with defined functions and operations, with micrometer, [15] and gigadalton scale multicomponent assemblies. [16,17] DNA origami objects have now graduated to dynamic movements with mechanical articulation or actuation programmed to respond to specific stimuli, including devices that open [18][19][20][21] or close [22] in response to target molecules (Figure 1). There are DNA origami devices that undergo multistage movement by strand-displacement reactions. [23,24] It is now possible for DNA origami devices to respond to electric fields [25,26] and light. [27,28] The ability to both program stimuli responsiveness and to create a multicomponent object able to communicate between the different components, to propagate information, andThe 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 s...

Computation-aided Design of Rod-Shaped Janus Base Nanopieces for Improved Tissue Penetration and Therapeutics Delivery

“…Unlike carbon nanotubes, JBNps are characterized by their unique DNA-mimicking chemical structure [18][19][20]. Furthermore, while they draw inspiration from DNA, JBNps diverge from DNA origami in that they do not comprise native DNA base pairs nor possess the conventional sugar-phosphate backbone; thereby, they are resistant to enzymatic cleavage [21,22]. In contrast to polymers, JBNps are assembled from thousands of small units through noncovalent interactions, giving them a distinct structural identity [23][24][25][26].…”

An Overview of Supramolecular Platforms Boosting Drug Delivery

“…Te use of DNA strands as scafolds yields diverse DNA "origami" nanostructures and establishes a mean to functionalize the origami tiles to achieve a desired activity [68,69]. Furthermore, substantial research eforts are dedicated to the engineering of 3D origami which self-assembles into supramolecular nanostructures exhibiting exiting properties [57,[70][71][72]. On the basis of the principle of DNA origami, the design of complex nanostructures characterized from tens to hundreds of peptide chains origami has not been reported yet [73].…”

Multi-Reconfigurable DNA Origami Nanolattice Driven by the Combination of Orthogonal Signals

“…Owing to the development of methods to fold DNA into artificial nanostructures and evolution of the chemical synthesis of custom oligonucleotides, DNA is now widely used as a programmable nanomaterial. , The early stage of the field of the structural DNA nanotechnology focused on the fabrication of static nanostructures with high precision in a robust manner. − In addition to that methodology, a variety of dynamic DNA nanodevices have been developed based on the differences in physical properties between single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). , ssDNA is often regarded as a flexible joint owing to its short persistence length (∼1.3 nm), whereas dsDNA has a persistence length of ∼50 nm − and is further bundled into rigid parts of the devices. Among the different types of methods implemented in structural DNA nanotechnology, scaffolded DNA origami is a powerful technique to obtain a desired two-/three-dimensional shape − and thus has been employed to construct reconfigurable nanodevices imitating normal-sized mechanical objects. − Successful attempts are represented by the development of DNA nanodevices and nanorobots exhibiting open-close motion, ,− sliding motion, ,, or rotary motion. − …”

“…Among the different types of methods implemented in structural DNA nanotechnology, scaffolded DNA origami is a powerful technique to obtain a desired two-/three-dimensional shape 11 − 14 and thus has been employed to construct reconfigurable nanodevices imitating normal-sized mechanical objects. 15 − 17 Successful attempts are represented by the development of DNA nanodevices and nanorobots exhibiting open-close motion, 15 , 18 − 25 sliding motion, 15 , 26 , 27 or rotary motion. 28 − 33 …”