Reconfiguring DNA Nanotube Architectures via Selective Regulation of Terminating Structures

Abstract

Molecular assemblies inside cells often undergo structural reconfiguration in response to stimuli to alter their function. Adaptive reconfiguration of cytoskeletal networks, for example, enables cellular shape change, movement, and cargo transport and plays a key role in driving complex processes such as division and differentiation. The cellular cytoskeleton is a self-assembling polymer network composed of simple filaments, so reconfiguration often occurs through the rearrangement of its component filaments' connectivities. DNA nanotubes have emerged as promising building blocks for constructing programmable synthetic analogs of cytoskeletal networks. Nucleating seeds can control when and where nanotubes grow, and capping structures can bind nanotube ends to stop growth. Such seeding and capping structures, collectively called termini, can organize nanotubes into larger architectures. However, these structures cannot be selectively activated or inactivated in response to specific stimuli to rearrange nanotube architectures, a key property of cytoskeletal networks. Here, we demonstrate how selective regulation of the binding affinity of DNA nanotube termini for DNA nanotube monomers or nanotube ends can direct the reconfiguration of nanotube architectures. Using DNA hybridization and strand displacement reactions that specifically activate or inactivate four orthogonal nanotube termini, we demonstrate that nanotube architectures can be reconfigured by selective addition or removal of distinct termini. Finally, we show how terminus activation could be a sensitive detector and amplifier of a DNA sequence signal. These results could enable the development of adaptive and multifunctional materials or diagnostic tools.

Cascaded Enzyme Reactions over a Three-Dimensional, Wireframe DNA Origami Scaffold

“… 43 Recent developments in dynamic nanoassembly also highlight the need to understand the impact of local environment and organization on enzyme activity. 36 , 44 , 45 …”

Reorganization of Self‐Assembled DNA‐Based Polymers using Orthogonally Addressable Building Blocks**

“…The high programmability and the possibility to predict in a straightforward way the thermodynamics of the involved non‐covalent hydrogen bond base pairings, together with the low cost of synthesis, has allowed the self‐assembly of unprecedented precise 2D and 3D structures, hydrogels, nanodevices and polymers from rationally designed synthetic DNA oligonucleotides [39–45] . Recently, the possibility to reconfigure these structures has also been demonstrated enabling dynamic DNA structures with potential adaptive behavior [46–51] …”

“…[39][40][41][42][43][44][45] Recently,t he possibility to reconfigure these structures has also been demonstrated enabling dynamic DNAs tructures with potential adaptive behavior. [46][47][48][49][50][51] Motivated by the above arguments and taking advantage of the addressability of DNAw es how here that synthetic nucleic acids are particularly suited for designing self-assembling dynamic polymer-like structures that can be easily reconfigured and reorganized by external inputs.T od ot his we have rationally designed monomer units that can be orthogonally addressed by different DNAr egulator strands and can be used to structurally reorganize the polymers between homopolymers,r andom co-polymers and two-tile and three-tile block co-polymers (Figure 1d). Thev ersatility of the systems presented in this study shows the ease at with DNA-based supramolecular polymers can be controlled using external triggers.…”

Reorganization of Self-Assembled DNA-Based Polymers Using Orthogonally Addressable Building Blocks

“…[39][40][41][42][43][44][45] Recently, the possibility to reconfigure these structures has also been demonstrated enabling dynamic DNA structures with potential adaptive behaviour. [46][47][48][49][50][51] Motivated by the above arguments and taking advantage of the addressability of DNA we show here that synthetic nucleic acids are particularly suited for designing selfassembling dynamic polymer-like structures that can be easily reconfigured and reorganized by external inputs. To do this we have rationally designed monomer units that can be orthogonally addressed by different DNA regulator strands and can be used to structurally reorganize the polymers between homopolymers, random co-polymers and diand tri-block co-polymers (Fig.…”