4,613 research outputs found
Algorithmic Self-Assembly of DNA: Theoretical Motivations and 2D Assembly Experiments
Biology makes things far smaller and more complex than anything produced by human engineering. The biotechnology revolution has for the first time given us the tools necessary to consider engineering on the molecular level. Research in DNA computation, launched by Len Adleman, has opened the door for experimental study of programmable biochemical reactions. Here we focus on a single biochemical mechanism, the self-assembly of DNA structures, that is theoretically sufficient for Turing-universal computation. The theory combines Hao Wang?s purely mathematical Tiling Problem with the branched DNA constructions of Ned Seeman. In the context of mathematical logic, Wang showed how jigsaw-shaped tiles can be designed to simulate the operation of any Turing Machine. For a biochemical implementation, we will need molecular Wang tiles. DNA molecular structures and intermolecular interactions are particularly amenable to design and are sufficient for the creation of complex molecular objects. The structure of individual molecules can be designed by maximizing desired and minimizing undesired Watson-Crick complementarity. Intermolecular interactions are programmed by the design of sticky ends that determine which molecules associate, and how. The theory has been demonstrated experimentally using a system of synthetic DNA double-crossover molecules that self-assemble into two-dimensional crystals that have been visualized by atomic force microscopy. This experimental system provides an excellent platform for exploring the relationship between computation and molecular self-assembly, and thus represents a first step toward the ability to program molecular reactions and molecular structures
Self-Healing Tile Sets
Biology provides the synthetic chemist with a tantalizing and frustrating challenge:
to create complex objects, defined from the molecular scale up to meters,
that construct themselves from elementary components, and perhaps
even reproduce themselves. This is the challenge of bottom-up fabrication.
The most compelling answer to this challenge was formulated in the early
1980s by Ned Seeman, who realized that the information carried by DNA
strands provides a means to program molecular self-assembly, with potential
applications including DNA scaffolds for crystallography [19] or for molecular
electronic circuits [15]. This insight opened the doors to engineering with the
rich set of phenomena available in nucleic acid chemistry [20]
On the Computational Power of DNA Annealing and Ligation
In [20] it was shown that the DNA primitives of Separate,
Merge, and Amplify were not sufficiently powerful to invert
functions defined by circuits in linear time. Dan Boneh et
al [4] show that the addition of a ligation primitive, Append, provides the missing power. The question becomes, "How powerful is ligation? Are Separate, Merge, and Amplify
necessary at all?" This paper proposes to informally explore
the power of annealing and ligation for DNA computation.
We conclude, in fact, that annealing and ligation alone are
theoretically capable of universal computation
Complexity of Restricted and Unrestricted Models of Molecular Computation
In [9] and [2] a formal model for molecular computing was
proposed, which makes focused use of affinity purification.
The use of PCR was suggested to expand the range of
feasible computations, resulting in a second model. In this
note, we give a precise characterization of these two models
in terms of recognized computational complexity classes,
namely branching programs (BP) and nondeterministic
branching programs (NBP) respectively. This allows us to
give upper and lower bounds on the complexity of desired
computations. Examples are given of computable and
uncomputable problems, given limited time
DNA Computing by Self-Assembly
Information and algorithms appear to be central to biological organization
and processes, from the storage and reproduction of genetic information to
the control of developmental processes to the sophisticated computations
performed by the nervous system. Much as human technology uses electronic
microprocessors to control electromechanical devices, biological
organisms use biochemical circuits to control molecular and chemical events.
The engineering and programming of biochemical circuits, in vivo and in
vitro, would transform industries that use chemical and nanostructured
materials. Although the construction of biochemical circuits has been
explored theoretically since the birth of molecular biology, our practical
experience with the capabilities and possible programming of biochemical
algorithms is still very young
Error Correction in DNA Computing: Misclassification and Strand Loss
We present a method of transforming an extract-based DNA computation that is error-prone into one that is relatively error-free. These improvements in error rates are achieved without the supposition of any improvements in the reliability of the underlying laboratory techniques. We assume that only two types of errors are possible: a DNA strand may be incorrectly processed or it may be lost entirely. We show to deal with each of these
errors individually and then analyze the tradeoff when both must be optimized simultaneously
How crystals that sense and respond to their environments could evolve
An enduring mystery in biology is how a physical entity simple enough to have arisen spontaneously could have evolved into the complex life seen on Earth today. Cairns-Smith has proposed that life might have originated in clays which stored genomes consisting of an arrangement of crystal monomers that was replicated during growth. While a clay genome is simple enough to have conceivably arisen spontaneously, it is not obvious how it might have produced more complex forms as a result of evolution. Here, we examine this possibility in the tile assembly model, a generalized model of crystal growth that has been used to study the self-assembly of DNA tiles. We describe hypothetical crystals for which evolution of complex crystal sequences is driven by the scarceness of resources required for growth. We show how, under certain circumstances, crystal growth that performs computation can predict which resources are abundant. In such cases, crystals executing programs that make these predictions most accurately will grow fastest. Since crystals can perform universal computation, the complexity of computation that can be used to optimize growth is unbounded. To the extent that lessons derived from the tile assembly model might be applicable to mineral crystals, our results suggest that resource scarcity could conceivably have provided the evolutionary pressures necessary to produce complex clay genomes that sense and respond to changes in their environment
Synthesis of crystals with a programmable kinetic barrier to nucleation
A central goal of chemistry is to fabricate supramolecular structures of defined function and composition. In biology, control of supramolecular synthesis is often achieved through precise control over nucleation and growth processes: A seed molecule initiates growth of a structure, but this growth is kinetically inhibited in the seed's absence. Here we show how such control can be systematically designed into self-assembling structures made of DNA tiles. These structures, "zig-zag ribbons," are designed to have a fixed width but can grow arbitrarily long. Under slightly supersaturated conditions, theory predicts that elongation is always favorable but that nucleation rates decrease exponentially with increasing width. We confirm experimentally that although ribbons of different widths have similar thermodynamics, nucleation rates decrease for wider ribbons. It is therefore possible to program the nucleation rate by choosing a ribbon width. The presence of a seed molecule, a stabilized version of the presumed critical nucleus, removes the kinetic barrier to nucleation of a ribbon. Thus, we demonstrate the ability to grow supramolecular structures from rationally designed seeds, while suppressing spurious nucleation. Control over DNA tile nucleation allows for proper initiation of algorithmic crystal growth, which could lead to the high-yield synthesis of micrometer-scale structures with complex programmed features. More generally, this work shows how a self-assembly subroutine can be initiated
Proofreading tile sets: Error correction for algorithmic self-assembly
For robust molecular implementation of tile-based algorithmic
self-assembly, methods for reducing errors must be developed. Previous
studies suggested that by control of physical conditions, such as
temperature and the concentration of tiles, errors (ε) can be reduced
to an arbitrarily low rate - but at the cost of reduced speed (r) for
the self-assembly process. For tile sets directly implementing blocked
cellular automata, it was shown that r ≈ βε^2 was optimal. Here, we
show that an improved construction, which we refer to as proofreading
tile sets, can in principle exploit the cooperativity of tile assembly reactions
to dramatically improve the scaling behavior to r ≈ βε and better.
This suggests that existing DNA-based molecular tile approaches may be
improved to produce macroscopic algorithmic crystals with few errors.
Generalizations and limitations of the proofreading tile set construction
are discussed
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