related. I am confident that at their interface great discoveries await those who seek them. ” (L.Adleman, [3]) 1. FOREWORD Natural computing is the field of research that investigates models and computational techniques inspired by nature and, dually, attempts to understand the world around us in terms of information processing. It is a highly interdisciplinary field that connects the natural sciences with computing science, both at the level of information technology and at the level of fundamental research, [98]. As a matter of fact, natural computing areas and topics come in many flavours, including pure theoretical research, algorithms and software applications, as well as biology, chemistry and physics experimental laboratory research. In this review we describe computing paradigms abstracted

Intelligent nanomechanical devices that operate in an autonomous fashion are of great theoretical and practical interest. Recent successes in building large scale DNA nanostructures, in constructing DNA mechanical devices, and in DNA computing provide a solid foundation for the next step forward: designing autonomous DNA mechanical devices capable of arbitrarily complex behavior. One prototype system towards this goal can be a DNA mechanical device that is capable of universal computation, by mimicking the operation of a universal Turing machine. Building on our prior theoretical designs and a prototype experimental construction of autonomous unidirectional DNA walking devices that move along linear tracks, we present in this paper the design of a nanomechanical DNA device that autonomously mimics the operation of a 2-state 5color universal Turing machine. Our autonomous nanomechanical device, which we call an Autonomous DNA Turing Machine, is thus capable of universal computation and hence complex translational motion which we define as universal translational motion.

My acquaintance with Ned Seeman began in the Caltech library sometime during 1992. At the time I was trying to design a DNA computer and was collecting papers in an attempt to learn all the biochemical tricks ever performed with DNA. Among the papers was Ned and Junghuei Chen’s beautiful construction of a DNA cube [1]. I had no idea how to harness such a marvel for computation – the diagrams explaining the cube were in a visual language that I could not parse and its static structure, once formed, did not seem to allow further information processing. However, I was in awe of the cube and wondered what kind of mad and twisted genius had conjured it. Ned’s DNA sculptures did turn out to have a relationship to computation. In 1994 Len Adleman’s creation of a DNA computer [2] showed that linear DNA self-assembly, together with operations such as PCR, could tackle NP-complete computational problems. Excited by this result, Erik Winfree quickly forged an amazing link that showed how the self-assembly of geometrical DNA objects, alone, can perform universal computation [3]. The

Abstract. Recent experimental progress in DNA lattice construction, DNA robotics, and DNA computing provides the basis for designing DNA cellular computing devices, i.e. autonomous nano-mechanical DNA computing devices embedded in DNA lattices. Once assembled, DNA cellular computing devices can serve as reusable, compact computing devices that perform (universal) computation, and programmable robotics devices that demonstrate complex motion. As a prototype of such devices, we recently reported the design of an Autonomous DNA Turing Machine, which is capable of universal sequential computation, and universal translational motion, i.e. the motion of the head of a single tape universal mechanical Turing machine. In this paper, we describe the design of an Autonomous DNA Cellular Automaton (ADCA), which can perform parallel universal computation by mimicking a one-dimensional (1D) universal cellular automaton. In the computation process, this device, embedded in a 1D DNA lattice, also demonstrates well coordinated parallel motion. The key technical innovation here is a molecular mechanism that synchronizes pipelined “molecular reaction waves”

Polymerases are a family of enzymes responsible for copying or replication of nucleic acids (DNA or RNA) templates and hence sustenance of life processes. In this paper, we present a method to exploit a strand-displacing polymerase φ29 as a driving force for nanoscale transportation devices. The principle idea behind the device is strong strand displacement ability of φ29, which can displace any DNA strand from its template while extending a primer hybridized to the template. This capability of φ29 is used to power the movement of a target nanostructure on a DNA track. The major advantage of using a polymerase driven nanotransportation device as compared to other existing nanorobotical devices is its speed. φ29 polymerase can travel at the rate of 2000 nucleotides per minute [1] at room temperature, which translates to approximately 680 nanometers per minute on a nanostructure. We also demonstrate transportation of a DNA cargo on a

Abstract. Practically all of life’s molecular processes, from chemical synthesis to replication, involve enzymes that carry out their functions through the catalysis of metastable fuels into waste products. Catalytic control of reaction rates will prove to be as useful and ubiquitous in DNA nanotechnology as it is in biology. Here we present experimental results on the control of the decay rates of a metastable DNA “fuel”. We show that the fuel complex can be induced to decay with a rate about 1600 times faster than it would decay spontaneously. The original DNA hybridization catalyst [15] achieved a maximal speed-up of roughly 30. The fuel complex discussed here can therefore serve as the basic ingredient for an improved DNA hybridization catalyst. As an example application for DNA hybridization catalysts, we propose a method for implementing arbitrary digital logic circuits. 1

A major challenge in nanoscience is the design of synthetic molecular devices that run autonomously and are programmable. DNA-based synthetic molecular devices have the advantage of being relatively simple to design and engineer, due to the predictable secondary structure of DNA nanostructures and the well-established biochemistry used to manipulate DNA nanostructures. We present the design of a class of DNAzyme based molecular devices that are autonomous, programmable, and further require no protein enzymes. The basic principle involved is inspired by a simple but ingenious molecular device due to Mao et al [25]. Our DNAzyme based designs include (1) a finite state automata device, DNAzyme FSA that executes finite state transitions using DNAzymes, (2) extensions to it including probabilistic automata and non-deterministic automata, (3) its application as a DNAzyme router for programmable routing of nanostructures on a 2D DNA addressable lattice, and (4) a medical-related application, DNAzyme doctor that provide transduction of nucleic acid expression: it can be programmed to respond to the underexpression or overexpression of various strands of RNA, with a response by release of an RNA.

The hybridization of complementary nucleic acid strands is the most basic of all reactions involving nucleic acids, but has a major limitation: the specificity of hybridization reactions depends critically on the lengths of the complementary pairs of strands and can drop (in the presence of other competing strands whose sequences are close to that of a given target strand) to very low values if the strands have sufficiently long length. This reduction in specificity of hybridization reactions occurs especially in the presence of noise in the form of other competing strands that have sequence segments identical to the target. This limitation in specificity significantly limits the scale and accuracy of biotechnology and nanotechnology applications which depend on hybridization reactions. Our paper develops techniques for ensuring specific high-fidelity DNA hybridization reactions for target strands of arbitrary length. Given an in vitro solution which contains various DNA strands with differing sequences, among them a particular known target DNA sequence s of relatively long length (say at least 60 to hundreds of bases), our goal is to bind to each subsequence segment of s with high specificity and

This Chapter overviews the past and current state of a selected part of the emerging research area of the field of DNA-based biomolecular devices. We particularly emphasize molecular devices that are: Autonomous: executing steps with no exterior mediation after starting, and Programmable: the tasks executed can be modified without entirely redesigning the nanostructure. We discuss work in this area that makes use of synthetic DNA to self-assemble into DNA nanostructure devices. Recently, there have been a series of impressive experimental results- which have taken the technology from a state of intriguing possibilities into demonstrated capabilities of quickly increasing scale. We discuss various such programmable molecular-scale devices that achieve: • computation, • 2D patterning, • amplified sensing, and • molecular or nano-scale transport. This article is written for a general audience, and particularly emphasizes the interdisciplinary aspects of this quickly evolving and exciting field. 1

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