Programming biomolecular self-assembly pathways. Nature

Department of Bioengineering, California Institute of Technology, Pasadena, California 91125, USA.
Nature (Impact Factor: 41.46). 02/2008; 451(7176):318-22. DOI: 10.1038/nature06451
Source: PubMed


In nature, self-assembling and disassembling complexes of proteins and nucleic acids bound to a variety of ligands perform intricate and diverse dynamic functions. In contrast, attempts to rationally encode structure and function into synthetic amino acid and nucleic acid sequences have largely focused on engineering molecules that self-assemble into prescribed target structures, rather than on engineering transient system dynamics. To design systems that perform dynamic functions without human intervention, it is necessary to encode within the biopolymer sequences the reaction pathways by which self-assembly occurs. Nucleic acids show promise as a design medium for engineering dynamic functions, including catalytic hybridization, triggered self-assembly and molecular computation. Here, we program diverse molecular self-assembly and disassembly pathways using a 'reaction graph' abstraction to specify complementarity relationships between modular domains in a versatile DNA hairpin motif. Molecular programs are executed for a variety of dynamic functions: catalytic formation of branched junctions, autocatalytic duplex formation by a cross-catalytic circuit, nucleated dendritic growth of a binary molecular 'tree', and autonomous locomotion of a bipedal walker.

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    • "For example, biomolecules themselves can mediate the formation of nanoparticles (NPs) or connect NPs to 1D, 2D, and 3D nanomaterials by using their functional groups[13,14]. In addition, biomolecules have the ability to form supramolecular nanostructures by the molecular self-assembly151617, and the formed supramolecular nanostructures can be the excellent building blocks or templates to further prepare functional nanomaterials[18,19]. Compared to the inorganic building blocks like metallic nanowires, biomolecules and their supra-structures preserve the unique nanoscale effect, molecular linear structure, physicochemical stability, self-assembly ability, and molecular recognition, and have being widely used in the fields of materials science, biophysical science, analytical science, and biomedical engineering[20]. Previously, several research groups have provided their perspectives and views on how to create biomolecule-based nanomaterials and nanostructures21222324. "
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    ABSTRACT: The combination of nanotechnology, biology, and bioengineering greatly improved the developments of nanomaterials with unique functions and properties. Biomolecules as the nanoscale building blocks play very important roles for the final formation of functional nanostructures. Many kinds of novel nanostructures have been created by using the bioinspired self-assembly and the subsequent binding with various nanoparticles. In this review, we summarized the studies on the fabrications and sensor applications of biomimetic nanostructures. The strategies for creating different bottom-up nanostructures by using biomolecules like DNA, protein, peptide, and virus, as well as microorganisms like bacteria and plant leaf are introduced. In addition, the potential applications of the synthesized biomimetic nanostructures for colorimetry, fluorescence, surface plasmon resonance, surface-enhanced Raman scattering, electrical resistance, electrochemistry, and quartz crystal microbalance sensors are presented. This review will promote the understanding of relationships between biomolecules/microorganisms and functional nanomaterials in one way, and in another way it will guide the design and synthesis of biomimetic nanomaterials with unique properties in the future.
    Full-text · Article · Jan 2016 · Materials
    • "This uses a simple seesaw gate, which is also called as DNA gate motif. Different DNA structures such as hairpins [15], [16], simple linear complexes [14] etc. can be used to perform a strand displacement operation. There are mainly two processes which drive a strand displacement system. "
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    ABSTRACT: Recently a great deal of interest has been shown by researchers on developing a bio-molecule based computer. The basic building blocks of such a computer are arithmetic units and memory. These units can be designed using Boolean logic gates as in the case of electronic circuits. Instead of using silicon based technology, Boolean logic gates can be generated from biological systems. One such system can be generated by a DNA reaction mechanism based on a reversible strand displacement process. A generalized pipeline architecture employing DNA reaction chain mechanism for the arithmetic operations such as addition, subtraction, multiplication, and division is discussed in this paper. A single control line is used in the pipeline array to control the different modes of operations. The primary functional blocks in a pipelined array are arithmetic unit and control unit. These units are made up of basic Boolean logic gates. To implement these gates, a DNA strand displacement process is employed. A set of integrating and amplifying gates are used in cascade with different threshold values to build different digital logic operations. The main advantage of such a system is that the arithmetic operations can be overlapped in the pipeline and thus a high speed operation is possible. Such a general Boolean model will be a step towards the development of a bio-computer. The ultimate goal of such a method is to design an automated system using logic gates, which make decisions within living cells.
    No preview · Conference Paper · Dec 2015
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    • ": Catalytic 3-arm junction formation. We show the catalytic 3-arm junction assembly process (originally demonstrated by Yin et al. [14] ), as enumerated by our software; the intended pathway is highlighted in red and purple. Boxes with rounded edges represent complexes—initial complexes have blue backgrounds, " transient " complexes have dashed borders (e.g. "
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    ABSTRACT: DNA strand displacement systems have proven themselves to be fertile substrates for the design of programmable molecular machinery and circuitry. Domain-level reaction enumerators provide the foundations for molecular programming languages by formalizing DNA strand displacement mechanisms and modeling interactions at the "domain" level - one level of abstraction above models that explicitly describe DNA strand sequences. Unfortunately, the most-developed models currently only treat pseudo-linear DNA structures, while many systems being experimentally and theoretically pursued exploit a much broader range of secondary structure configurations. Here, we describe a new domain-level reaction enumerator that can handle arbitrary non-pseudoknotted secondary structures and reaction mechanisms including association and dissociation, 3-way and 4-way branch migration, and direct as well as remote toehold activation. To avoid polymerization that is inherent when considering general structures, we employ a time-scale separation technique that holds in the limit of low concentrations. This also allows us to "condense" the detailed reactions by eliminating fast transients, with provable guarantees of correctness for the set of reactions and their kinetics. We hope that the new reaction enumerator will be used in new molecular programming languages, compilers, and tools for analysis and verification that treat a wider variety of mechanisms of interest to experimental and theoretical work. We have implemented this enumerator in Python, and it is included in the DyNAMiC Workbench Integrated Development Environment.
    Full-text · Article · May 2015
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