Paul W. K. Rothemund

Bio: Paul W. K. Rothemund is an academic researcher from California Institute of Technology. The author has contributed to research in topics: DNA origami & DNA nanotechnology. The author has an hindex of 34, co-authored 55 publications receiving 12772 citations. Previous affiliations of Paul W. K. Rothemund include University of California, Santa Barbara & University of Southern California.

Folding DNA to create nanoscale shapes and patterns

Abstract: 'Bottom-up fabrication', which exploits the intrinsic properties of atoms and molecules to direct their self-organization, is widely used to make relatively simple nanostructures. A key goal for this approach is to create nanostructures of high complexity, matching that routinely achieved by 'top-down' methods. The self-assembly of DNA molecules provides an attractive route towards this goal. Here I describe a simple method for folding long, single-stranded DNA molecules into arbitrary two-dimensional shapes. The design for a desired shape is made by raster-filling the shape with a 7-kilobase single-stranded scaffold and by choosing over 200 short oligonucleotide 'staple strands' to hold the scaffold in place. Once synthesized and mixed, the staple and scaffold strands self-assemble in a single step. The resulting DNA structures are roughly 100 nm in diameter and approximate desired shapes such as squares, disks and five-pointed stars with a spatial resolution of 6 nm. Because each oligonucleotide can serve as a 6-nm pixel, the structures can be programmed to bear complex patterns such as words and images on their surfaces. Finally, individual DNA structures can be programmed to form larger assemblies, including extended periodic lattices and a hexamer of triangles (which constitutes a 30-megadalton molecular complex).

Algorithmic self-assembly of DNA Sierpinski triangles.

Abstract: Algorithms and information, fundamental to technological and biological organization, are also an essential aspect of many elementary physical phenomena, such as molecular self-assembly. Here we report the molecular realization, using two-dimensional self-assembly of DNA tiles, of a cellular automaton whose update rule computes the binary function XOR and thus fabricates a fractal pattern—a Sierpinski triangle—as it grows. To achieve this, abstract tiles were translated into DNA tiles based on double-crossover motifs. Serving as input for the computation, long single-stranded DNA molecules were used to nucleate growth of tiles into algorithmic crystals. For both of two independent molecular realizations, atomic force microscopy revealed recognizable Sierpinski triangles containing 100–200 correct tiles. Error rates during assembly appear to range from 1% to 10%. Although imperfect, the growth of Sierpinski triangles demonstrates all the necessary mechanisms for the molecular implementation of arbitrary cellular automata. This shows that engineered DNA self-assembly can be treated as a Turing-universal biomolecular system, capable of implementing any desired algorithm for computation or construction tasks.

Self-assembly of carbon nanotubes into two-dimensional geometries using DNA origami templates

Abstract: A central challenge in nanotechnology is the parallel fabrication of complex geometries for nanodevices. Here we report a general method for arranging single-walled carbon nanotubes in two dimensions using DNA origami—a technique in which a long single strand of DNA is folded into a predetermined shape. We synthesize rectangular origami templates (~75 nm × 95 nm) that display two lines of single-stranded DNA ‘hooks’ in a cross pattern with ~6 nm resolution. The perpendicular lines of hooks serve as sequence-specific binding sites for two types of nanotubes, each functionalized non-covalently with a distinct DNA linker molecule. The hook-binding domain of each linker is protected to ensure efficient hybridization. When origami templates and DNA-functionalized nanotubes are mixed, strand displacement-mediated deprotection and binding aligns the nanotubes into cross-junctions. Of several cross-junctions synthesized by this method, one demonstrated stable field-effect transistor-like behaviour. In such organizations of electronic components, DNA origami serves as a programmable nanobreadboard; thus, DNA origami may allow the rapid prototyping of complex nanotube-based structures.

Solution of a 20-Variable 3-SAT Problem on a DNA Computer

Abstract: oligonucleotide probes immobilized in polyacrylamide gel‐filled glass modules. Information-carrying DNA strands are moved through the modules by electrophoresis. Strands with subsequences complementary to those of the immobilized probes hybridize and are retained in the module; strands without complementary subsequences pass through the module relatively unhindered (21). Captured strands are released from the probes by running electrophoresis at a temperature higher than the melting temperature of the probe/complement duplex. Released strands may be transported via electrophoresis to new modules for further separations. Using electrophoresis to transport DNA strands between gel-filled glass modules results in a computer that is “dry” and potentially automatable. Because covalent bonds are neither made nor broken during separations, DNA strands and glass modules are potentially reusable for multiple computations.

The program-size complexity of self-assembled squares

Abstract: Molecular self-assembly gives rise to a great diversity of complex forms, from crystals and DNA helices to microtubules and holoenzymes. We study a formal model of pseudocrystalline self-assembly, called the Tile Assembly Model, in which a tile may be added to the growing object when the total interaction strength with its neighbors exceeds a parameter Τ. This model has been shown to be Turing-universal. Thus, self-assembled objects can be studied from the point of view of computational complexity. Here, we define the program size complexity of an NxN square to be the minimum number of distinct tiles required to self-assemble the square and no other objects. We study this complexity under the Tile Assembly Model and find a dramatic decrease in complexity, from N^2 tiles to O(log N) tiles, as Τ is increased from 1 (where bonding is noncooperative) to 2 (allowing cooperative bonding). Further, we find that the size of the largest square uniquely produced by a set of n tiles grows faster than any computable function.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Nano-sized transition-metal oxides as negative-electrode materials for lithium-ion batteries

Abstract: Rechargeable solid-state batteries have long been considered an attractive power source for a wide variety of applications, and in particular, lithium-ion batteries are emerging as the technology of choice for portable electronics. One of the main challenges in the design of these batteries is to ensure that the electrodes maintain their integrity over many discharge-recharge cycles. Although promising electrode systems have recently been proposed, their lifespans are limited by Li-alloying agglomeration or the growth of passivation layers, which prevent the fully reversible insertion of Li ions into the negative electrodes. Here we report that electrodes made of nanoparticles of transition-metal oxides (MO, where M is Co, Ni, Cu or Fe) demonstrate electrochemical capacities of 700 mA h g(-1), with 100% capacity retention for up to 100 cycles and high recharging rates. The mechanism of Li reactivity differs from the classical Li insertion/deinsertion or Li-alloying processes, and involves the formation and decomposition of Li2O, accompanying the reduction and oxidation of metal nanoparticles (in the range 1-5 nanometres) respectively. We expect that the use of transition-metal nanoparticles to enhance surface electrochemical reactivity will lead to further improvements in the performance of lithium-ion batteries.

Folding DNA to create nanoscale shapes and patterns

Abstract: 'Bottom-up fabrication', which exploits the intrinsic properties of atoms and molecules to direct their self-organization, is widely used to make relatively simple nanostructures. A key goal for this approach is to create nanostructures of high complexity, matching that routinely achieved by 'top-down' methods. The self-assembly of DNA molecules provides an attractive route towards this goal. Here I describe a simple method for folding long, single-stranded DNA molecules into arbitrary two-dimensional shapes. The design for a desired shape is made by raster-filling the shape with a 7-kilobase single-stranded scaffold and by choosing over 200 short oligonucleotide 'staple strands' to hold the scaffold in place. Once synthesized and mixed, the staple and scaffold strands self-assemble in a single step. The resulting DNA structures are roughly 100 nm in diameter and approximate desired shapes such as squares, disks and five-pointed stars with a spatial resolution of 6 nm. Because each oligonucleotide can serve as a 6-nm pixel, the structures can be programmed to bear complex patterns such as words and images on their surfaces. Finally, individual DNA structures can be programmed to form larger assemblies, including extended periodic lattices and a hexamer of triangles (which constitutes a 30-megadalton molecular complex).

Molecular self-assembly and nanochemistry: A chemical strategy for the synthesis of nanostructures

Abstract: Molecular self-assembly is the spontaneous association of molecules under equilibrium conditions into stable, structurally well-defined aggregates joined by noncovalent bonds. Molecular self-assembly is ubiquitous in biological systems and underlies the formation of a wide variety of complex biological structures. Understanding self-assembly and the associated noncovalent interactions that connect complementary interacting molecular surfaces in biological aggregates is a central concern in structural biochemistry. Self-assembly is also emerging as a new strategy in chemical synthesis, with the potential of generating nonbiological structures with dimensions of 1 to 10(2) nanometers (with molecular weights of 10(4) to 10(10) daltons). Structures in the upper part of this range of sizes are presently inaccessible through chemical synthesis, and the ability to prepare them would open a route to structures comparable in size (and perhaps complementary in function) to those that can be prepared by microlithography and other techniques of microfabrication.

Self-assembly of DNA into nanoscale three-dimensional shapes

Abstract: Molecular self-assembly offers a 'bottom-up' route to fabrication with subnanometre precision of complex structures from simple components. DNA has proved to be a versatile building block for programmable construction of such objects, including two-dimensional crystals, nanotubes, and three-dimensional wireframe nanopolyhedra. Templated self-assembly of DNA into custom two-dimensional shapes on the megadalton scale has been demonstrated previously with a multiple-kilobase 'scaffold strand' that is folded into a flat array of antiparallel helices by interactions with hundreds of oligonucleotide 'staple strands'. Here we extend this method to building custom three-dimensional shapes formed as pleated layers of helices constrained to a honeycomb lattice. We demonstrate the design and assembly of nanostructures approximating six shapes-monolith, square nut, railed bridge, genie bottle, stacked cross, slotted cross-with precisely controlled dimensions ranging from 10 to 100 nm. We also show hierarchical assembly of structures such as homomultimeric linear tracks and heterotrimeric wireframe icosahedra. Proper assembly requires week-long folding times and calibrated monovalent and divalent cation concentrations. We anticipate that our strategy for self-assembling custom three-dimensional shapes will provide a general route to the manufacture of sophisticated devices bearing features on the nanometre scale.