Programming biomolecular self-assembly pathways

Yin, Peng; Choi, Harry M. T.; Calvert, Colby R.; Pierce, Niles A.

doi:10.1038/nature06451

Cited by 1,417 publications

(1,199 citation statements)

References 37 publications

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“…This precisely controlled, long-range transport could lead to the development of systems that could be programmed and routed by instructions encoded in the nucleotide sequences of the track and motor. Such systems might be used to create molecular assembly lines modelled on the ribosome.An effective linear molecular motor must traverse its track without dissociating [1][2][3][4][5][6][7]10,12 and run unidirectionally without external intervention [4][5][6][7][8][9][10][11][12] . Directionality may be imposed by the sequential addition of DNA instructions 1-3 or, for autonomous motors, by modifying the track sites that have been visited 5,6,12 , by coupling motion to a unidirectional reaction cycle 4,9,12 or by coordinating the conformation changes of different parts of the motor 11,12 .…”

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“…Directionality may be imposed by the sequential addition of DNA instructions 1-3 or, for autonomous motors, by modifying the track sites that have been visited 5,6,12 , by coupling motion to a unidirectional reaction cycle 4,9,12 or by coordinating the conformation changes of different parts of the motor 11,12 . DNA motors that satisfy all these criteria have typically been demonstrated on tracks that allow only 1-3 steps, although a stochastic DNA 'spider' with many legs has been shown to move longer distances by biased diffusion 17 along a 100 nm track 18 .…”

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“…Controlled motion at the nanoscale can be achieved by using Watson-Crick base-pairing to direct the assembly and operation of a molecular transport system consisting of a track, a motor [1][2][3][4][5][6][7][8][9][10][11][12] and fuel [13][14][15] , all made from DNA. Here, we assemble a 100-nm-long DNA track on a two-dimensional scaffold 16 , and show that a DNA motor loaded at one end of the track moves autonomously and at a constant average speed along the full length of the track, a journey comprising 16 consecutive steps for the motor.…”

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Direct observation of stepwise movement of a synthetic molecular transporter

et al. 2011

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Controlled motion at the nanoscale can be achieved by using Watson-Crick base-pairing to direct the assembly and operation of a molecular transport system consisting of a track, a motor 1-12 and fuel [13][14][15] , all made from DNA. Here, we assemble a 100-nm-long DNA track on a two-dimensional scaffold 16 , and show that a DNA motor loaded at one end of the track moves autonomously and at a constant average speed along the full length of the track, a journey comprising 16 consecutive steps for the motor. Real-time atomic force microscopy allows direct observation of individual steps of a single motor, revealing mechanistic details of its operation. This precisely controlled, long-range transport could lead to the development of systems that could be programmed and routed by instructions encoded in the nucleotide sequences of the track and motor. Such systems might be used to create molecular assembly lines modelled on the ribosome.An effective linear molecular motor must traverse its track without dissociating [1][2][3][4][5][6][7]10,12 and run unidirectionally without external intervention [4][5][6][7][8][9][10][11][12] . Directionality may be imposed by the sequential addition of DNA instructions 1-3 or, for autonomous motors, by modifying the track sites that have been visited 5,6,12 , by coupling motion to a unidirectional reaction cycle 4,9,12 or by coordinating the conformation changes of different parts of the motor 11,12 . DNA motors that satisfy all these criteria have typically been demonstrated on tracks that allow only 1-3 steps, although a stochastic DNA 'spider' with many legs has been shown to move longer distances by biased diffusion 17 along a 100 nm track 18 .We have investigated the motion of a simple directional and processive motor fuelled by DNA hydrolysis 6 along an extended track consisting of a one-dimensional array of single-stranded attachment sites (stators), separated by 6 nm. An extended track of 15 identical stators, flanked with special start and stop stators 6 , was assembled on a rectangular DNA origami tile measuring 100 nm × 70 nm (ref. 16; Fig. 1, Supplementary Figs S1, S2). The tile comprises a 7,249-nucleotide (nt) single-stranded DNA template (genome of bacteriophage M13) hybridized to short synthetic staple strands such that the final tile consists of a raft of 24 parallel double helices tethered by the crossover of staples. Two tile designs were used. The helices of tile type A are crosslinked at 16 bp intervals, creating slight underwinding (10.7 bp per turn), which is expected to lead to a global right-handed twisting of the tile 19 . Tile type B is designed to reduce this twist: the average distance between crossovers is 15.6 bp (giving 10.4 bp per turn). The centre and ends of each staple are positioned on opposite surfaces of the tile. Selected staples were extended to include either the 22-nt stator sequence at the 5 ′ end or a hairpin at the centre 16 (Fig. 1a). Stators hybridized to complementary motor strands are visible in atomic force microscope (AFM) images...

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Direct observation of stepwise movement of a synthetic molecular transporter

et al. 2011

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“…A beautiful example is provided by the creation of DNA origami [12][13][14] , or of other DNA-based microstructures, such as molecular spiders and nanorobots [15][16][17] . Here various target structures can be achieved by favouring the base pairing of specific DNA regions, which embody the struts of the desired construct.…”

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Self-assembling knots of controlled topology by designing the geometry of patchy templates

et al. 2015

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The self-assembly of objects with a set of desired properties is a major goal of material science and physics. A particularly challenging problem is that of self-assembling structures with a target topology. Here we show by computer simulation that one may design the geometry of string-like rigid patchy templates to promote their efficient and reproducible self-assembly into a selected repertoire of non-planar closed folds including several knots. In particular, by controlling the template geometry, we can direct the assembly process so as to strongly favour the formation of constructs tied in trefoil or pentafoil, or even of more exotic torus knots. Polydisperse and racemic mixtures of helical fragments of variable composition add further tunability in the topological self-assembly we discovered. Our results should be relevant to the design of new ways to synthesize molecular knots, which may prove, for instance, to be efficient cargo-carriers due to their mechanical stability.

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“…DNA, because of its programmability and biocompatibility, has emerged as the substrate of choice to build complex structures [4 -11], or to compute and actuate elaborate functions [8,[12][13][14][15][16][17][18][19][20][21][22]. In particular, strand displacement has proved an exquisite mechanism to orchestrate the hybridization of DNA strands [23][24][25][26][27][28][29]. In this mechanism, a strand of DNA (the output) is selectively displaced from a gate by the action of one or several strands (the inputs) [30 -32].…”

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Scaling down DNA circuits with competitive neural networks

Genot

Fujii

Rondelez

2013

J. R. Soc. Interface.

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DNA has proved to be an exquisite substrate to compute at the molecular scale. However, nonlinear computations (such as amplification, comparison or restoration of signals) remain costly in term of strands and are prone to leak. Kim et al. showed how competition for an enzymatic resource could be exploited in hybrid DNA/enzyme circuits to compute a powerful nonlinear primitive: the winner-take-all (WTA) effect. Here, we first show theoretically how the nonlinearity of the WTA effect allows the robust and compact classification of four patterns with only 16 strands and three enzymes. We then generalize this WTA effect to DNA-only circuits and demonstrate similar classification capabilities with only 23 strands.

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Programming biomolecular self-assembly pathways

Cited by 1,417 publications

References 37 publications

Direct observation of stepwise movement of a synthetic molecular transporter

Direct observation of stepwise movement of a synthetic molecular transporter

Self-assembling knots of controlled topology by designing the geometry of patchy templates

Scaling down DNA circuits with competitive neural networks

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