Molecular Robots Research Articles

Recent Progress of Magnetically Actuated DNA Micro/Nanorobots.

In the past few decades, the field of DNA origami-based micro/nanotechnology has developed dramatically and spawned attention increasingly, as its high integrality, rigid structure, and excellent resistance ability to enzyme digestion. Many two-dimensional and three-dimensional DNA nanostructures coordinated with optical, chemical, or magnetic triggers have been designed and assembled, extensively used as versatile templates for molecular robots, nanosensors, and intracellular drug delivery. The magnetic field has been widely regarded as an ideal driving and operating system for micro/nanomaterials, as it does not require high-intensity lasers like light control, nor does it need to change the chemical composition similar to chemical activation. Herein, we review the recent achievements in the induction and actuation of DNA origami-based nanodevices that respond to magnetic fields. These magnetic actuation-based DNA nanodevices were regularly combined with magnetic beads or gold nanoparticles and applied to generate single-stranded scaffolds, assemble various DNA nanostructures, and purify specific DNA nanostructures. Moreover, they also produced artificial magnetism or moved regularly driven by external magnetic fields to explain deeper scientific issues.

Construction of Artificial Cell-type Molecular Robots

Construction of Artificial Cell-type Molecular Robots

A DNA Molecular Robot that Autonomously Walks on the Cell Membrane to Drive Cell Motility

AbstractSynthetic molecular robots can execute sophisticated molecular tasks at nanometer resolution. However, a molecular robot capable of controlling cellular behavior remains unexplored. Herein, we report a self‐propelled DNA robot operating on the cell membrane to control the migration of a cell. Driven by DNAzyme catalytic activity, the DNA robot could autonomously and stepwise move on the membrane‐floating cell‐surface receptors in a stochastic manner and simultaneously trigger the receptor‐dimerization to activate downstream signaling for cell motility. The cell membrane‐associated continuous motion and operation of a DNA robot allowed for the ultrasensitive regulation of MET/AKT signaling and cytoskeleton remodeling to enhance cell migration. Finally, we designed distinct conditional DNA robots to orthogonally manipulate the cell migration in a coculture of mixed cell populations. We have developed a novel strategy to engineer a cell‐driving molecular robot, representing a promising avenue for precise cell manipulation with nanoscale resolution.

A DNA Molecular Robot that Autonomously Walks on the Cell Membrane to Drive Cell Motility.

Synthetic molecular robots can execute sophisticated molecular tasks at nanometer resolution. However, a molecular robot capable of controlling cellular behavior remains unexplored. Herein, we report a self-propelled DNA robot operating on the cell membrane to control the migration of a cell. Driven by DNAzyme catalytic activity, the DNA robot could autonomously and stepwise move on the membrane-floating cell-surface receptors in a stochastic manner and simultaneously trigger the receptor-dimerization to activate downstream signaling for cell motility. The cell membrane-associated continuous motion and operation of a DNA robot allowed for the ultrasensitive regulation of MET/AKT signaling and cytoskeleton remodeling to enhance cell migration. Finally, we designed distinct conditional DNA robots to orthogonally manipulate the cell migration in a coculture of mixed cell populations. We have developed a novel strategy to engineer a cell-driving molecular robot, representing a promising avenue for precise cell manipulation with nanoscale resolution.

Innenrücktitelbild: A DNA Molecular Robot that Autonomously Walks on the Cell Membrane to Drive Cell Motility (Angew. Chem. 50/2021)

Ein molekularer DNA-Roboter wurde entwickelt, der sich autonom auf der Zellmembran bewegt, um die Zellmotilität zu steuern. Der DNA-Roboter kann sich autonom und schrittweise auf den Zelloberflächenrezeptoren auf stochastische Weise fortbewegen, um so die Rezeptordimerisierung auszulösen und nachgeschaltete Signalwege zu aktivieren, die das gewünschte Zellverhalten regulieren, wie Hong-Hui Wang, Zhou Nie et al. in ihrem Forschungsartikel auf S. 26291 berichten.

Inside Back Cover: A DNA Molecular Robot that Autonomously Walks on the Cell Membrane to Drive Cell Motility (Angew. Chem. Int. Ed. 50/2021)

A DNA molecular robot autonomously walking on a cell membrane to drive cell motility has been developed. The DNA robot can autonomously and stepwise locomote on the membrane-floating cell-surface receptors in a stochastic manner to simultaneously trigger receptor dimerization to activate downstream signal pathways regulating desired cellular behavior, as reported by Hong-Hui Wang, Zhou Nie, and co-workers in their Research Article on page 26087.

Determination of urinary N-acetylneuraminic acid for early diagnosis of lung cancer by a boric acid covalently functionalized lanthanide MOFs and its intelligent visual molecular robot application

In this work, a boric acid covalently functionalized lanthanide MOF (Ln-MOF) sensor was constructed for the first time to monitor of urinary N-acetylneuraminic acid (NANA) to early diagnose of lung cancer, NANA can be used as biomarker of lung cancer. Considering that the specific binding affinity between boronic acid group and cis-diol can probably cause special influence towards the fluorescence of Ln-MOF, a boric-acid-functionalized Ln-MOF (B-EuMOF) sensor was first designed by covalent modification, which is proved to be an effective ratiometric fluorescent sensor of NANA, a urinary biomarker of lung cancer containing cis-diol. This designed NANA sensor shows special enrichment capacity, high selectivity and sensitivity, fast response, excellent reusability and more important, the ratiometric sensing result can be clearly distinguished by naked eye. Based on the luminescent sensing property of B-EuMOF towards NANA and the capture function of boric acid group, a molecular robot system which can monitor lung cancer at early stage is constructed. In this molecular robot system, boronic acid group serves as the actuator using ‘functional-hand’ to grasp NANA for the molecular robots. The fluorescence of B-EuMOF (I470 nm/I614 nm) act as the sensor of the molecular robots. And the processor is constructed by combinational logic gates (INHIBIT and AND) which can control the molecular robots by logical operation of fluorescence response of B-EuMOF towards NANA. This work proposes first example of Ln-MOFs based molecular robot and what’s more, paves new way for the combination of fluorescent sensor and intelligent molecular devices.

Switching ON of Transcription-Translation System Using GUV Fusion by Co-supplementation of Calcium with Long-Chain Polyethylene Glycol.

Giant unilamellar vesicles (GUVs) have been used as a material for bottom-up synthetic biology. However, due to the semi-permeability of the membrane, the need for methods to fuse GUVs has increased. To this aim, methods that are simple and show low leakage during fusion are important. In this study, we report a method of GUV fusion by a divalent cation (Ca2+ ) enhanced with a long chain polyethylene glycol (PEG20k). The methods showed significant GUV fusion without leakage of internal components of GUVs and maintained cell-free transcription-translation ability inside the GUVs without external supplementation of macromolecules. We demonstrate that the Ca-PEG method can be applied for switching ON of transcription-translation in GUVs in a fusion-dependent manner. The method developed here can be applied to extend bottom-up synthetic biology and molecular robotics that use GUVs as a chassis.

Improving the method of grinding substances to a nanostate

At the end of the 20th century, a theory was put forward, suggesting that with the help of universal molecular robots, it would be possible to collect any objects from improvised molecules according to a given program. The process was called "nanotechnology". The term «nano» comes from the Greek word "nanos" (dwarf) and corresponds to one billionth of a unit. Nanotechnology is the most modern and advanced direction of science and technology development. The excavations of archaeologists prove that nanomaterials were widely used in the ancient world, for instance, the Mayan civilization used clay, the structure of which contained nanofragments. In ancient Mesopotamia, weapons and glasses painted with metal nanoparticles were produced. In 2007, the state corporation "Russian Corporation of Nanotechnologies" was officially registered in Russia. For the implementation of processes occurring at the molecular level, it was necessary to develop methods for grinding substances to design new substances with super-efficient properties. Due to the introduction of nanotechnology to science, technology, medicine and other fields, there will be significant changes in people's lives. Recently, the problem of introducing nanotechnology into medicine and pharmacology to obtain effective medicines of superhigh quality is especially urgent. One of the main issues nanotechnologists are facing is the problem of grinding substances to a nanostate. The existing processes of grinding substances often require not only high energy costs and labor intensity, but also do not allow achieving the desired result. The article presents an original method of grinding various substances to the molecular level by grinding the molecules of the substance with the particles of the complex "carbyne-cyclic ion-ligand" during the rotation of the complex under the influence of an external electric field. The conducted laboratory tests confirm the effectiveness of the proposed method.

Engineering control circuits for molecular robots using synthetic biology.

The integration of molecular robots and synthetic biology allows for the creation of sophisticated behaviors at the molecular level. Similar to the synergy between bioelectronics and soft robotics, synthetic biology provides control circuitry for molecular robots. By encoding perception-action modules within synthetic circuits, molecular machines can advance beyond repeating tasks to the incorporation of complex behaviors. In particular, cell-free synthetic biology provides biomolecular circuitry independent of living cells. This research update reviews the current progress in using synthetic biology as perception-action control modules in robots from molecular robots to macroscale robots. Additionally, it highlights recent developments in molecular robotics and cell-free synthetic biology and suggests their combined use as a necessity for future molecular robot development.

Construction of Cell-like Molecular Robots Based on DNA Nanotechnology

Construction of Cell-like Molecular Robots Based on DNA Nanotechnology

Recent Advances in Liposome-Based Molecular Robots.

A molecular robot is a microorganism-imitating micro robot that is designed from the molecular level and constructed by bottom-up approaches. As with conventional robots, molecular robots consist of three essential robotics elements: control of intelligent systems, sensors, and actuators, all integrated into a single micro compartment. Due to recent developments in microfluidic technologies, DNA nanotechnologies, synthetic biology, and molecular engineering, these individual parts have been developed, with the final picture beginning to come together. In this review, we describe recent developments of these sensors, actuators, and intelligence systems that can be applied to liposome-based molecular robots. First, we explain liposome generation for the compartments of molecular robots. Next, we discuss the emergence of robotics functions by using and functionalizing liposomal membranes. Then, we discuss actuators and intelligence via the encapsulation of chemicals into liposomes. Finally, the future vision and the challenges of molecular robots are described.

Robotic DNA Nanostructures.

Over the past decade, DNA nanotechnology has spawned a broad variety of functional nanostructures tailored toward the enabled state at which applications are coming increasingly in view. One of the branches of these applications is in synthetic biology, where the intrinsic programmability of the DNA nanostructures may pave the way for smart task-specific molecular robotics. In brief, the synthesis of the user-defined artificial DNA nano-objects is based on employing DNA molecules with custom lengths and sequences as building materials that predictably assemble together by obeying Watson–Crick base pairing rules. The general workflow of creating DNA nanoshapes is getting more and more straightforward, and some objects can be designed automatically from the top down. The versatile DNA nano-objects can serve as synthetic tools at the interface with biology, for example, in therapeutics and diagnostics as dynamic logic-gated nanopills, light-, pH-, and thermally driven devices. Such diverse apparatuses can also serve as optical polarizers, sensors and capsules, autonomous cargo-sorting robots, rotary machines, precision measurement tools, as well as electric and magnetic-field directed robotic arms. In this review, we summarize the recent progress in robotic DNA nanostructures, mechanics, and their various implementations.

Environment-Sensitive Intelligent Self-Reproducing Artificial Cell with a Modification-Active Lipo-Deoxyribozyme.

As a supramolecular micromachine with information flow, a giant vesicle (GV)-based artificial cell that exhibits a linked proliferation between GV reproduction and internal DNA amplification has been explored in this study. The linked proliferation is controlled by a complex consisting of GV membrane-intruded DNA with acidic amphiphilic catalysts, working overall as a lipo-deoxyribozyme. Here, we investigated how a GV-based artificial cell containing this lipo-deoxyribozyme responds to diverse external and internal environments, changing its proliferative dynamics. We observed morphological changes (phenotypic expression) in GVs induced by the addition of membrane precursors with different intervals of addition (starvation periods). First, we focused on a new phenotype, the “multiple tubulated” form, which emerged after a long starvation period. Compared to other forms, the multiple tubulated form is characterized by a larger membrane surface with a heavily cationic charge. A second consideration is the effect of the chain length of encapsulated DNA on competitive proliferation. The competitive proliferation among three different species of artificial cells containing different lengths of DNA was investigated. The results clearly showed a distinct intervention in the proliferation dynamics of the artificial cells with each other. In this sense, our GV-based artificial cell can be regarded as an intelligent supramolecular machine responding to external and internal environments, providing a new concept for developing molecular machines and robotics.

Mechanical Stimulation‐Induced Orientation of Gliding Microtubules in Confined Microwells

AbstractBiomolecular motors are the smallest natural machines that can convert chemical energy into mechanical work with much higher energy efficiencies compared to man‐made machineries. Nowadays, reconstructed biomolecular motors, such as microtubules–kinesin, are successfully utilized for nanotechnological applications, e.g., in nanotransportation, parallel computation, molecular robotics, and so on. However, stochastic nature of their motion poses a limitation to their applications, which is difficult to control particularly under spatial constraints. In this work, top‐down and bottom‐up approaches are combined to address this problem in a gliding assay of microtubules. Through mechanical stimulation of the motile microtubule filaments, parallelization of the filaments is demonstrated concurrently in hundreds of microwells. The orientation of plenty of motile microtubules in confined space should further accelerate nanotechnological applications of biomolecular motors.

Correction to: Special Issue on Molecular Robotics

The article “Special Issue on Molecular Robotics”, written by Satoshi Murata was originally published electronically on the publisher's internet portal (currently SpringerLink) on 18th May 2020 with open access.

Special Issue on Molecular Robotics

Special Issue on Molecular Robotics

Distributed Computing Theory for Molecular Robot Systems

Distributed computation consists of local computations and their interactions. We consider a molecular robot system as a distributed system composed of mobile computing entities with very weak capabilities, i.e., computing entities are anonymous (indistinguishable), oblivious (memory-less), and uniform (following a common local computation rule). The key property of such a distributed system is self-organization. In this survey, we first introduce shape formation by mobile computing entities and present characterizations of formable shapes. We then consider global behavior realized by shapes of a distributed system. We demonstrate general computational power of mobile computing entities in terms of computing languages and predicates. Finally, we demonstrate dynamic behavior, such as locomotion and search, realized by a sequence of shapes.

Synchronous operation of biomolecular engines.

Biomolecular motor systems are the smallest natural machines with an ability to convert chemical energy into mechanical work with remarkably high efficiency. Such attractive features enabled biomolecular motors to become classic tools in soft matter research over the past decade. For designing suitably engineered biomimetic systems, the biomolecular motors can potentially be used as molecular engines that can transform energy and ensure great advantages for the construction of bio-nanodevices and molecular robots. From the optimization of their prolonged lifetime to coordinate them into highly complex and ordered structures, enormous efforts have been devoted to make them useful in the synthetic environment. Synchronous operation of the biomolecular engines is one of the key criteria to coordinate them into certain different patterns, which depends on the local interaction of biomolecular motors. Utilizing chemical and physical stimuli, synchronization of biomolecular motor systems has become possible, which allows them to coordinate into different higher ordered patterns with different modes of functionality. Recently, programmed synchronous operation of the biomolecular engines has also been demonstrated, using a smart biomaterial to build up swarms reminiscent of nature. Here, we review the recent progress in the synchronized operation of biomolecular motors in engineered systems to explicitly program their interaction and further their applications. Such developments in the coordination of biomolecular motors have opened a broad way to explore the construction of future autonomous molecular machines and robots based on synchronization of biomolecular engines.

Photolithographic shape control of DNA hydrogels by photo-activated self-assembly of DNA nanostructures.

We report a photolithographic method for the shape control of DNA hydrogels based on photo-activated self-assembly of Y-shaped DNA nanostructures (Y-motifs). To date, various methods to control the shape of DNA hydrogels have been developed to enhance the functions of the DNA hydrogel system. However, photolithographic production of shape-controlled DNA hydrogels formed through the self-assembly of DNA nanostructures without the use of radical polymerizations has never been demonstrated, although such a method is expected to be applied for the shape-control of DNA hydrogels encapsulating sensitive biomolecules, such as proteins. In this study, we used a photo-activated linker to initiate the self-assembly of Y-motifs, where the cross-linker DNA was at first inactive but was activated after UV light irradiation, resulting in the formation of shape-controlled DNA hydrogels only at the UV-exposed area produced by photomasks. We believe that this method will be applied for the construction of biohybrid machines, such as molecular robots and artificial cells that contain intelligent biomolecular devices, such as molecular sensors and computers.