Report of Contributions

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Statistical Mechanics and Computation of DNA

Self-Assembly

Report of Contributions

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Statistical Mech … / Report of Contributions (no title)

Contribution ID: 250 Type: not specified

(no title)

Primary author:

Prof. KRAMER, Fred (Public Health Research Institute)

March 19, 2023 Page 1

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Statistical Mech … / Report of Contributions Finicky and Sloppy Molecular Bea …

Finicky and Sloppy Molecular Beacons

Wednesday, 25 May 2011 17:00 (1h 15m)

Molecular beacons are hairpin-shaped oligonucleotide probes that undergo a fluorogenic conformational change upon binding to PCR amplicons. They can be labeled with differently colored fluorophores, enabling multiplex assays to be carried out in sealed reaction tubes. They can be designed to be “finicky”, so that they only bind to

amplicons from a single species, or they can be designed to be “sloppy”, so that they bind to amplicons from many different species. The set of melting temperatures obtained from the probe-target hybrids that are formed with a limited set of differently colored, sloppy molecular beacon probes uniquely identifies which bacterial species is present in a clinical sample (from a list of more than a hundred species). Alternatively, the unique set of colors that appear in a screening assay containing as many as 35

combinatorially color-coded, finicky molecular beacon probes identifies the infectious agent. The use of molecular

beacons in digital PCR formats will enable many different targets in a single clinical sample to be simultaneously identified and quantitated.

Presenter:

Prof. KRAMER, Fred (Public Health Research Institute)

Session Classification: Ferry session

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Statistical Mech … / Report of Contributions Sequence, shape, function: a prim …

Sequence, shape, function: a primer to DNA origami

Wednesday, 25 May 2011 18:45 (1h 15m)

Advanced molecular self-assembly with ‘DNA origami’ offers a unique route for building custom shaped high-complexity objects that are commensurate in size to biological

macromolecules. DNA origami objects can be used as platforms for placing, orienting, and even manipulating biological molecules in user defined ways. Thus, DNA origami objects can not only help improve existing experimental methods in the molecular biosciences but they also open completely new avenues of exploration.

In our laboratory we have set out to develop custom ‘nano’

instrumentation based on DNA origami that complements single-molecule-level methods for observing and manipulating biological macromolecules. Among other goals, we seek to enable the study of adhesive interactions between

biomolecules in unprecedented detail. We also aim to develop tools for unraveling the conformational dynamics of proteins at work in novel ways. More long term, we hope to be able to create a biologically inspired nanotechnology including devices that are capable of performing complex tasks such as enzymatic catalysis or molecular transport for human purposes.

In my lecture I will focus on an introduction to DNA origami, our near-term applications, and report about some of our efforts in analyzing and improving molecular self-assembly reactions with DNA origami.

Primary author:

Prof. DIETZ, Hendrik (Technische Universität München)

Presenter:

Prof. DIETZ, Hendrik (Technische Universität München)

Session Classification: Ferry session

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Statistical Mech … / Report of Contributions Self-assembly of DNA into nanos …

Self-assembly of DNA into nanoscale three-dimensional shapes

Thursday, 26 May 2011 09:15 (45 minutes)

I will present a general method for solving a key challenge for nanotechnology: programmable self-assembly of complex, three-dimensional nanostructures. Previously, scaffolded DNA origami had been used to build arbitrary flat shapes 100 nm in diameter and almost twice the mass of a ribosome. We have succeeded in building custom three-dimensional structures that can be conceived as stacks of nearly flat layers of DNA. Successful extension from two-dimensions to three-dimensions in this way depended critically on calibration of folding conditions. This general capability for building complex, three-dimensional nanostructures will pave the way for the manufacture of sophisticated devices bearing features on the nanometer scale.

Primary author:

Prof. SHIH, William (Harvard Medical School)

Presenter:

Prof. SHIH, William (Harvard Medical School)

Session Classification: Statistical mechanics

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Statistical Mech … / Report of Contributions Assembly of single-walled carbon …

Assembly of single-walled carbon nanotubes on DNA-origami templates through streptavidin-biotin

interaction

I present work where we propose a novel method for the controlled positioning of carbon nanotubes on DNA

self-assembled structures. The method is based on the use of streptavidin (STV)–biotin interaction. Precise assembly of both a single CNT and CNT cross-junctions on DNA-origami templates with relatively high yield is demonstrated. The results thus make an essential contribution to the toolbox of nanowire assembly on DNA origami templates.

Primary author:

Prof. TÖRMÄ, Päivi (Aalto University)

Presenter:

Prof. TÖRMÄ, Päivi (Aalto University)

Session Classification: Statistical mechanics

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Statistical Mech … / Report of Contributions Dynamical nanosystems made fro …

Dynamical nanosystems made from DNA, RNA, and occasionally a few other components

Saturday, 28 May 2011 11:15 (45 minutes)

The highly predictable interactions between DNA or RNA molecules have been utilized for the construction of a large variety of molecular structures and devices. For instance, the recently developed DNA origami technique facilitates the molecular assembly of two- and even three-dimensional nano-objects with almost arbitrary shape - and with nanometric precision. These structures can be used as molecular scaffolds for the arrangement of nanoscale objects such as nanoparticles or proteins into specific geometries.

Such assemblies may help to exploit distance or geometry dependent - chemical or physical - interactions between these components. In addition to the realization of static molecular nanostructures one of the major promises of molecular nanotechnology is the creation of dynamic molecular assemblies such as molecular switches, actuators, and biochemical circuits. A few examples of such assemblies will be described, and also our recent attempts to

characterize these structures with fluorescence microscopic techniques.

Primary author:

Prof. SIMMEL, Friedrich (TU Munchen)

Presenter:

Prof. SIMMEL, Friedrich (TU Munchen)

Session Classification: Synthesis

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Statistical Mech … / Report of Contributions Free-form design of 3D DNA nan …

Free-form design of 3D DNA nanostructures using vHelix for Autodesk Maya

CAD software for the design of 3D DNA origami nanostructures have been reported previously. In caDNAno by Shawn Douglas, and the more recent CanDo package by Castro and co-workers the focus has been on designing structures where parallel helices are packed in a square-, or honeycomb-lattice. In our recent efforts in building a DNA nanopore, there has been a need for a design software that allows a little bit more freedom in the orientations of the double helices with respect to each other. To this end we have implemented a plug-in for the 3D modeling software Autodesk Maya. Here we present this plug-in, called vHelix, and demonstrate how it can be used to easily design previously untested DNA geometries.

Primary author:

Prof. HÖGBERG, Björn (Karolinska Institute)

Presenter:

Prof. HÖGBERG, Björn (Karolinska Institute)

Session Classification: Statistical mechanics

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Statistical Mech … / Report of Contributions Microfluidic tools for DNA analys …

Microfluidic tools for DNA analysis, manipulation and separation

We present our recent studies concerning micro-and nanofluidic devices that are capable of detecting, manipulating and separating single DNAs with different lengths and conformations [1,2] and with complexed molecules such as polymerases or chemotherapeutics [3,4].

The first device consists of a straight microchannel structured with an array of non-conducting posts, which create dielectrophoretic traps when a voltage is applied.

The escape process of DNA molecules migrating through the structure can be modelled using Kramers’ rate theory and quantitative values for DNA polarizability are extractable.

The same principle can be exploited to separate single linear and supercoiled DNA molecules by length and conformation within less than 4 minutes.

The central element of the second device is a 3D-structured microfluidic channel with a bended constriction that reduces the channel height to about 670 nm. At this barrier, dielectrophoretic forces selectively deflect DNA with a bound agent (proteins or antibiotics) and let the

uncomplexed DNA fragments pass unhindered. As the device operates continuously, no actual separation time exists and the separated samples can be immediately collected or post-processed. The result of the separation can be observed in real-time allowing for an on-line optimization of the parameters of separation during operation. As a

proof-of-principle, we demonstrate the separation of DNA molecules with different length and DNA/polymerase as well as DNA/Actinomycin D complexes from uncomplexed DNA.

[1] J. Regtmeier, T.T. Duong, R. Eichhorn, D. Anselmetti, A.

Ros, Analytical Chemistry 79, 3925-3932 (2007) [2] J. Regtmeier, R. Eichhorn, L. Bogunovic, A. Ros, D.

Anselmetti, Analytical Chemistry 82, 7141-7149 (2010) [3] M. Everwand, D. Anselmetti, J. Regtmeier, Proceedings of the µTAS

2010, 19-21 (2010)

[4] M. Everwand, R. Eichhorn, J. Regtmeier, D. Anselmetti, in preparation

Primary author:

Dr BOGUNOVIC, Lukas (Universität Bielefeld)

Presenter:

Dr BOGUNOVIC, Lukas (Universität Bielefeld)

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Statistical Mech … / Report of Contributions Microfluidic tools for DNA analys …

Session Classification: Statistical mechanics

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Statistical Mech … / Report of Contributions Thermodynamics of RNA hybridi …

Thermodynamics of RNA hybridization inferred from out of equilibrium unzipping experiments

We have recently developed a methodology to infer the free energy of hybridization of DNA with a single molecule technique (Huguet et al., PNAS 107, 15431 (2010)). It consists in unzipping a molecule of DNA of a few thousands of base pairs with optical tweezers. These pulling

experiments provide a force vs. distance curve that is analyzed to obtain the free energy of formation of the Nearest-Neighbor motifs. However, this technique is only valid for quasistatic pulling experiments. We have extended our technique to out of equilibrium experiments, in which the force vs. distance curves are not quasistatic anymore.

So we are able to analyze the data obtained from pulling experiments on RNA, which exhibits much more hysteresis than DNA. The main advantage of this technique is that it

circumvents the problems of bulk experiments such as aggregation of molecules or self-catalization of biomolecules at certain salt concentrations or pH. The results pave the way to establish the single-molecule unzipping experiments as a reliable technique to extract the free energy of formation of the motifs of biomolecules.

Primary author:

Dr HUGUET, Josep Maria (Universitat de Barcelona)

Presenter:

Dr HUGUET, Josep Maria (Universitat de Barcelona)

Session Classification: Statistical mechanics

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Statistical Mech … / Report of Contributions Coarse-grained modelling of DNA …

Coarse-grained modelling of DNA and DNA self-assembly

We have recently proposed a coarse-grained model of DNA [1]

which captures much of the thermodynamic and physical changes associated with DNA duplex formation from isolated single strands, in particular representing double-stranded hybridization, hairpin formation and single-stranded stacking consistently for the first time. Despite this, the model is suciently simple to allow the study of processes occurring on long timescales, and as such provides access to the physics of nanostructure formation and nanomachine operation. Here we present the model, and explore

applications to DNA tweezers, a two-footed DNA walker and DNA origami. [1] T. E. Ouldridge, A. A. Louis, and J. P. K.

Doye, Phys. Rev. Lett. 104, 178101 (2010).

Primary author:

Dr OULDRIDGE, Thomas (Oxford University)

Presenter:

Dr OULDRIDGE, Thomas (Oxford University)

Session Classification: Statistical mechanics

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Statistical Mech … / Report of Contributions Toward a Programmable Chemist …

Toward a Programmable Chemistry with Strand Displacement Cascades

Friday, 27 May 2011 09:15 (45 minutes)

What challenges must be overcome before engineers can design molecules and their interactions with ease? The ideas of abstraction and modularity allowed the creation of software and hardware systems of extreme complexity consisting of millions of lines of code and hundreds of millions of

transistors. Mimicking software and hardware engineering, an approach to the molecular challenge is to find a basic set of interactions that can be composed in various ways without interference, and then create a hierarchy of modules of increasing complexity leading to the desired higher-level function.

Nucleic acids are a very promising candidate for the underlying molecular substrate for such modular systems, and have been used to construct a variety of nanoscale structures, mechanical nanomachines, sensors, and information processing devices. Nucleic acids are also biologically compatible and potentially capable of

interfacing with existing cellular machinery, hinting at the eventual possibility of therapeutic applications.

“Strand-displacement cascades” describes the technology combining toehold-mediated branch migration,

toehold blocking by hybridization, and toehold exchange, to enable coupled cascades of strand displacement reactions.

The promise of this technology is that all the necessary nucleic acid interactions can be systematically programmed using a few simple rules, and composed into hierarchically assembled complex systems.

My talk will review developments both in the theory and experimental practice of strand displacement cascades.

Computer theoretic abstractions have had a key role in thinking about strand displacement cascades: chemical reaction networks, process algebras, digital circuits, state machines, as well as special-purpose algebras have all been harnessed as organizing principles. I will review the utility of such abstractions for the engineering of complex networks of molecular interactions, focusing particularly on chemical reaction networks as an intermediate abstraction layer (eg how digital circuits can be compiled to chemical reaction networks which in turn can be compiled to strand displacement cascades). I will also review the art of designing domain sequences, as well as the available modeling and simulation tools, and outline our first steps toward experimentally realizing certain dynamical systems such as oscillators that may become parts of future embedded

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Statistical Mech … / Report of Contributions Toward a Programmable Chemist …

control modules. In the final part of the talk I will review the substantial remaining engineering challenges.

Primary author:

Prof. SOLOVEICHIK, David (University of Washington)

Presenter:

Prof. SOLOVEICHIK, David (University of Washington)

Session Classification: Computation

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Statistical Mech … / Report of Contributions The termination problem in self- …

The termination problem in self-assembly

We consider the algorithmic problem of determining if a given self-assembly system is terminating, that is, if an unbounded growth may happen or not. We prove that this question is undecidable even in the simple tiling model of self-assembly, by showing that no algorithm is able to determine if a given set of Wang tiles can form on the plane an infinite path where consecutive tiles match with each other. We also consider the analogous problem of determining whether given tiles can form a correctly tiled loop, and prove its undecidability.

Primary author:

Prof. KARI, Jarkko (University of Turku)

Presenter:

Prof. KARI, Jarkko (University of Turku)

Session Classification: Computation

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Statistical Mech … / Report of Contributions DNA codeword design: theory and …

DNA codeword design: theory and application

Finding large sets of single DNA strands that do not crosshybridize to themselves or to their complements is an important problem in DNA computing, self-assembly, DNA memories and phylogenetic analyses, because of their error correction and prevention properties. The problem is in itself NP-complete, even in very simplified versions using any single reasonable measure that approximates the Gibbs energy, thus practically excluding the possibility of finding any efficient procedure to find maximal sets efficiently. After a quick survey of advances in this area in the last few years, we focus on a novel

combinatorial/geometric framework to analyze this problem.

In this framework, codeword design is reduced to finding large sets of strands maximally separated in DNA spaces and therefore the size of such sets depends on the geometry of these DNA spaces. We present a new general technique to embed DNA spaces in Euclidean spaces and thus, among others, reduce the word design problem to the well known sphere packing problem in information theory. The embedding sheds some insights into the geometry of DNA spaces by enabling a quantitative analysis via well established approximations of the Gibbs energy, namely the nearest neighbor model of duplex formation. The main tool is an efficiently computable combinatorial approximation which is also a mathematical metric. As illustration, we show two applications to produce provably nearly optimal codeword sets (modulo the goodness of the Gibbs energy approximation) and a new methodology for phylogenetic analyses in Biology. We conclude with a brief discussion of some qualitative properties of the Gibbs energy landscapes for short DNA oligo spaces.

Primary author:

Prof. GARZON, Max (The University of Memphis)

Presenter:

Prof. GARZON, Max (The University of Memphis)

Session Classification: Computation

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Statistical Mech … / Report of Contributions On Recycling and its Limits in Str …

On Recycling and its Limits in Strand Displacement Systems

We consider recycling, or reuse of molecules, in chemical reaction systems and their DNA strand displacement realizations. Recycling happens when a product of one reaction is a reactant in a later reaction. Recycling has the benefits of reducing consumption, or waste, of molecules and of avoiding fuel depletion. We will describe a binary counter that recycles molecules efficiently while incurring just a moderate slowdown compared to alternative counters that do not recycle strands. This counter is an n-bit

binary reflecting gray code counter; it advances through 2ˆn states while consuming just O(n) molecules. In the strand displacement realization of this counter, the waste—total number of nucleotides of the DNA strands consumed—is O(nˆ3), while alternative counters have waste proportional to 2ˆn. We also show limits to the potential for recycling strands. In particular, our n-bit counter fails to work

correctly when many copies of the species that represent the state (bits) of the counter are present initially.

Primary author:

Prof. CONDON, Anne (University of British Columbia)

Presenter:

Prof. CONDON, Anne (University of British Columbia)

Session Classification: Computation

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Statistical Mech … / Report of Contributions Building a DNA brain

Building a DNA brain

Not long after Adleman showed that DNA can serve as a computing substrate, Baum proposed using DNA to build an associative memory larger than the brain. Attempts to bring these ideas to fruition have been hindered by requirements for enzymes or manual experimental steps. Here our interest is in DNA strand displacement circuits that can perform neural network computation autonomously. We make use of a simple DNA gate architecture that has recently allowed experimental scale-up of multilayer digital circuits. We developed a systematic procedure for transforming arbitrary linear threshold circuits (an artificial neural network model) into DNA strand displacement cascades. We demonstrated our approach by successfully implementing several small neural networks, including a Hopfield associative memory that has four fully connected artificial neurons. This tiny DNA brain can play a game called read your mind” (a variation of20 questions”) with a human. As an alternative to Baum’s goal, our results suggest that DNA strand displacement cascades could be used to embed

“intelligence” within autonomous chemical systems, capable of recognizing patterns of molecular events, making decisions and responding to the environment.

Primary author:

Dr QIAN, Lulu (Caltech)

Presenter:

Dr QIAN, Lulu (Caltech)

Session Classification: Computation

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Statistical Mech … / Report of Contributions A Design Framework for Carbon …

A Design Framework for Carbon Nanotube Circuits Affixed on DNA Origami Tiles

Recent years have witnessed a burst of experimental activity concerning algorithmic self-assembly of nanostructures, motivated at least in part by the potential of this approach as a radically new manufacturing technology. Our specific interest is in the self-assembly of Carbon-Nanotube Field Effect Transistor (CNFET) circuits. In the present work, we propose a generic framework for the design of CNFET circuits comprising a “universal” set of 14 functionalised DNA origami tiles. With a proper selection of “glues” on the tiles, any desired CNFET circuit can be self-assembled from this basis.

Primary author:

Dr CZEIZLER, Eugen (Aalto University)

Presenter:

Dr CZEIZLER, Eugen (Aalto University)

Session Classification: Computation

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Statistical Mech … / Report of Contributions Growth of arbitrarily shaped metal …

Growth of arbitrarily shaped metal nanoparticles templated by DNA origami

The directed metallization of DNA origami nanostructures could give

rise to self-assembling materials with novel optical and electronic

properties. We show that three-dimensional (3D) DNA origami structures

can be converted into gold nanoparticles of designed shapes by a two-

step metallization process: Positively charged 1.4 nm gold nanoclusters adsorb to the negatively charged DNA objects followed by

electroless deposition of gold from solution. Using this strategy,

nanoparticles with a narrow size distribution and controllable shapes

and dimensions are created. This site-directed metallization constitutes a general and easy route for shape-defined growth of

continuously metallized objects, such as nanorods, nanodonuts, cuboids

and kites of controlled sizes and lengths.

Primary author:

Prof. LIEDL, Tim (LMU München)

Presenter:

Prof. LIEDL, Tim (LMU München)

Session Classification: Synthesis

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Statistical Mech … / Report of Contributions Algorithmic Self-Assembly of DN …

Algorithmic Self-Assembly of DNA: Theory and Experiment

Self-assembly is a fundamental process in the

self-organization of biological as well as non-biological structures. Passive self-assembly of molecular units, being driven just by thermodynamic binding energies and the geometrical structure of the molecules, would seem to be the simplest case to study – but it can be remarkably

complicated. In fact, in a model of generalized crystal growth abstracted as the self-assembly of Wang tiles, passive self-assembly can be shown to be Turing universal.

This leads to a number of theoretical observations: complex shapes that have concise algorithmic descriptions can be self-assembled from a small number of parts; these self-assembled structures can perform error correction during growth and can self-heal after damage; and as a simple form of self-replication, algorithmic crystals could provide an abiological example of Darwinian evolution. In our lab, we have been working to demonstrate these principles experimentally, using molecular Wang tiles constructed from DNA.

Primary author:

Prof. WINFREE, Erik (Caltech)

Presenter:

Prof. WINFREE, Erik (Caltech)

Session Classification: Synthesis

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Statistical Mech … / Report of Contributions On the theory of cost and benefit - …

Report of Contributions

Statistical Mechanics and Computation of DNA

Self-Assembly