26th International Conference on DNA Computing and Molecular Programming, DNA 26, September 14-17, 2020, Oxford, UK (Virtual Conference)

The routing of a DNA-origami scaffold strand is often modelled as an Eulerian circuit of an Eulerian graph in combinatorial models of DNA origami design. The knot type of the scaffold strand dictates the feasibility of an Eulerian circuit to be used as the scaffold route in the design. Motivated by the topology of scaffold routings in 3D DNA origami, we investigate the knottedness of Eulerian circuits on surface-embedded graphs. We show that certain graph embeddings, checkerboard colorable, always admit unknotted Eulerian circuits. On the other hand, we prove that if a graph admits an embedding in a torus that is not checkerboard colorable, then it can be re-embedded so that all its non-intersecting Eulerian circuits are knotted. For surfaces of genus greater than one, we present an infinite family of checkerboard-colorable graph embeddings where there exist knotted Eulerian circuits. 2012 ACM Subject Classification Mathematics of computing → Discrete mathematics

[1]  Erik Winfree,et al.  Thermodynamic Analysis of Interacting Nucleic Acid Strands , 2007, SIAM Rev..

[2]  Lulu Qian,et al.  Efficient Turing-Universal Computation with DNA Polymers , 2010, DNA.

[3]  Dana Randall Phase Transitions in Sampling Algorithms and the Underlying Random Structures , 2010, SWAT.

[4]  Marta Z. Kwiatkowska,et al.  PRISM 4.0: Verification of Probabilistic Real-Time Systems , 2011, CAV.

[5]  Joseph S. B. Mitchell,et al.  Locked and Unlocked Chains of Planar Shapes , 2010, Discret. Comput. Geom..

[6]  Ashish Goel,et al.  Combinatorial optimization problems in self-assembly , 2002, STOC '02.

[7]  Erik Winfree,et al.  Time Complexity of Computation and Construction in the Chemical Reaction Network-Controlled Tile Assembly Model , 2016, DNA.

[8]  Daniel Jackson,et al.  Alloy: a language and tool for exploring software designs , 2019, Commun. ACM.

[9]  David F. Anderson,et al.  Continuous Time Markov Chain Models for Chemical Reaction Networks , 2011 .

[10]  Luca Cardelli,et al.  Central Limit Model Checking , 2018, ACM Trans. Comput. Log..

[11]  Robert F. Johnson,et al.  Impossibility of Sufficiently Simple Chemical Reaction Network Implementations in DNA Strand Displacement , 2019, UCNC.

[12]  D. Barford,et al.  The structure and mechanism of protein phosphatases: insights into catalysis and regulation. , 1998, Annual review of biophysics and biomolecular structure.

[13]  Jehoshua Bruck,et al.  Neural network computation with DNA strand displacement cascades , 2011, Nature.

[14]  Mario Gleirscher,et al.  Isabelle/SACM: Computer-Assisted Assurance Cases with Integrated Formal Methods , 2019, IFM.

[15]  Conrad Steenberg,et al.  NUPACK: Analysis and design of nucleic acid systems , 2011, J. Comput. Chem..

[16]  Erik Winfree,et al.  Active self-assembly of algorithmic shapes and patterns in polylogarithmic time , 2013, ITCS '13.

[17]  H. Rice Classes of recursively enumerable sets and their decision problems , 1953 .

[18]  Parosh Aziz Abdulla,et al.  Model Checking Parameterized Systems , 2018, Handbook of Model Checking.

[19]  François Fages,et al.  Strong Turing Completeness of Continuous Chemical Reaction Networks and Compilation of Mixed Analog-Digital Programs , 2017, CMSB.

[20]  Paul G. Spirakis,et al.  On the Transformation Capability of Feasible Mechanisms for Programmable Matter , 2017, ICALP.

[21]  Shawn M. Douglas,et al.  Self-assembly of DNA into nanoscale three-dimensional shapes , 2009, Nature.

[22]  Harry M. T. Choi,et al.  Programming biomolecular self-assembly pathways , 2008, Nature.

[23]  Samir Mitragotri,et al.  Layered self-assemblies for controlled drug delivery: A translational overview. , 2020, Biomaterials.

[24]  J. SantaLucia,et al.  The thermodynamics of DNA structural motifs. , 2004, Annual review of biophysics and biomolecular structure.

[25]  H. Schaeffer,et al.  MP1: a MEK binding partner that enhances enzymatic activation of the MAP kinase cascade. , 1998, Science.

[26]  L M Adleman,et al.  Molecular computation of solutions to combinatorial problems. , 1994, Science.

[27]  T. Hunter,et al.  The Protein Kinase Complement of the Human Genome , 2002, Science.

[28]  Shawn M. Douglas,et al.  Folding DNA into Twisted and Curved Nanoscale Shapes , 2009, Science.

[29]  W. Hughes,et al.  Multi-Arm Junctions for Dynamic DNA Nanotechnology. , 2017, Journal of the American Chemical Society.

[30]  J. Yasuda,et al.  A mammalian scaffold complex that selectively mediates MAP kinase activation. , 1998, Science.

[31]  Luca Cardelli,et al.  Design and analysis of DNA strand displacement devices using probabilistic model checking , 2012, Journal of The Royal Society Interface.

[32]  Christian Scheideler,et al.  Computing by Programmable Particles , 2019, Distributed Computing by Mobile Entities.

[33]  M. Elowitz,et al.  A synthetic oscillatory network of transcriptional regulators , 2000, Nature.

[34]  A. Turberfield,et al.  Programmable energy landscapes for kinetic control of DNA strand displacement , 2014, Nature Communications.

[35]  A. Turberfield,et al.  Design of hidden thermodynamic driving for non-equilibrium systems via mismatch elimination during DNA strand displacement , 2020, Nature Communications.

[36]  Erik Winfree,et al.  Universal Computation and Optimal Construction in the Chemical Reaction Network-Controlled Tile Assembly Model , 2015, DNA.

[37]  Matthew R. Lakin,et al.  Bioinformatics Applications Note Systems Biology Visual Dsd: a Design and Analysis Tool for Dna Strand Displacement Systems , 2022 .

[38]  Ryuji Kawano,et al.  Synthetic Ion Channels and DNA Logic Gates as Components of Molecular Robots. , 2018, Chemphyschem : a European journal of chemical physics and physical chemistry.

[39]  Hieu Bui,et al.  Localized DNA Hybridization Chain Reactions on DNA Origami. , 2018, ACS nano.

[40]  E. Winfree Simulations of Computing by Self-Assembly , 1998 .

[41]  Eric F. Wieschaus,et al.  Pulsed contractions of an actin–myosin network drive apical constriction , 2009, Nature.

[42]  Chengde Mao,et al.  Self-assembly of hexagonal DNA two-dimensional (2D) arrays. , 2005, Journal of the American Chemical Society.

[43]  Sarfraz Khurshid,et al.  CRN++: Molecular programming language , 2018, Natural Computing.

[44]  Constantine G. Evans Crystals that Count! Physical Principles and Experimental Investigations of DNA Tile Self-Assembly , 2014 .

[45]  Luca Cardelli,et al.  Programmable chemical controllers made from DNA. , 2013, Nature nanotechnology.

[46]  Nadine L. Dabby,et al.  Synthetic Molecular Machines for Active Self-Assembly: Prototype Algorithms, Designs, and Experimental Study , 2013 .

[47]  Eric F. Wieschaus,et al.  folded gastrulation, cell shape change and the control of myosin localization , 2005, Development.

[48]  Matthew J. Patitz An introduction to tile-based self-assembly and a survey of recent results , 2014, Natural Computing.

[49]  J. Collins,et al.  Construction of a genetic toggle switch in Escherichia coli , 2000, Nature.

[50]  Lila Kari,et al.  Negative Interactions in Irreversible Self-assembly , 2010, Algorithmica.

[51]  Robert D. Barish,et al.  Three-helix bundle DNA tiles self-assemble into 2D lattice or 1D templates for silver nanowires. , 2005, Nano letters.

[52]  Thomas E. Ouldridge,et al.  High rates of fuel consumption are not required by insulating motifs to suppress retroactivity in biochemical circuits , 2017, 1708.01792.

[53]  Chris Thachuk,et al.  Probabilistic Model Checking for Biology , 2014, Software Systems Safety.

[54]  Pekka Orponen,et al.  Synthesizing Minimal Tile Sets for Patterned DNA Self-assembly , 2010, DNA.

[55]  Erik Winfree,et al.  Enzyme-free nucleic acid dynamical systems , 2017, Science.

[56]  Matthew J. Patitz,et al.  Asynchronous signal Passing for Tile Self-assembly: Fuel Efficient Computation and Efficient assembly of Shapes , 2012, Int. J. Found. Comput. Sci..

[57]  Friedrich C Simmel,et al.  Robustness of localized DNA strand displacement cascades. , 2014, ACS nano.

[58]  Robert T. Schweller,et al.  Self-assembly of shapes at constant scale using repulsive forces , 2018, Natural Computing.

[59]  Jack H. Lutz,et al.  Runtime Fault Detection in Programmed Molecular Systems , 2017, ACM Trans. Softw. Eng. Methodol..

[60]  David Eisenstat,et al.  A simple population protocol for fast robust approximate majority , 2007, Distributed Computing.

[61]  Erik D. Demaine,et al.  Simulation of Programmable Matter Systems Using Active Tile-Based Self-Assembly , 2019, DNA.

[62]  Eduardo D Sontag,et al.  The energy costs of insulators in biochemical networks. , 2013, Biophysical journal.

[63]  Robert M. Dirks,et al.  An autonomous polymerization motor powered by DNA hybridization , 2007, Nature Nanotechnology.

[64]  Robert T. Schweller,et al.  Covert Computation in Self-Assembled Circuits , 2019, ICALP.

[65]  John C Wooley,et al.  Catalyzing Inquiry at the Interface of Computing and Biology , 2005 .

[66]  P. Rothemund Folding DNA to create nanoscale shapes and patterns , 2006, Nature.

[67]  Andrew Winslow,et al.  Tight Bounds for Active Self-Assembly Using an Insertion Primitive , 2015, Algorithmica.

[68]  Erik D. Demaine,et al.  Reconfiguration of Cube-Style Modular Robots Using O(logn) Parallel Moves , 2008, ISAAC.

[69]  Shawn M. Douglas,et al.  A Logic-Gated Nanorobot for Targeted Transport of Molecular Payloads , 2012, Science.

[70]  Robert T. Schweller,et al.  Self-Assembly of Any Shape with Constant Tile Types using High Temperature , 2018, ESA.

[71]  D. Y. Zhang,et al.  Engineering Entropy-Driven Reactions and Networks Catalyzed by DNA , 2007, Science.

[72]  T. Kurtz The Relationship between Stochastic and Deterministic Models for Chemical Reactions , 1972 .

[73]  Xiao Wang,et al.  Rapid Prototyping of Wireframe Scaffolded DNA Origami using ATHENA , 2020, bioRxiv.

[74]  Erik Winfree,et al.  Proofreading Tile Sets: Error Correction for Algorithmic Self-Assembly , 2003, DNA.

[75]  I. Herskowitz MAP kinase pathways in yeast: For mating and more , 1995, Cell.

[76]  N. Seeman,et al.  A Proximity-Based Programmable DNA Nanoscale Assembly Line , 2010, Nature.

[77]  Lulu Qian,et al.  Parallel and Scalable Computation and Spatial Dynamics with DNA-Based Chemical Reaction Networks on a Surface , 2014, DNA.

[78]  Erik D. Demaine,et al.  Linear Reconfiguration of Cube-Style Modular Robots , 2007, ISAAC.

[79]  Pieter Rein ten Wolde,et al.  Energy dissipation and noise correlations in biochemical sensing. , 2014, Physical review letters.

[80]  Andrew Winslow,et al.  Complexities for High-Temperature Two-Handed Tile Self-assembly , 2017, DNA.

[81]  C. Marshall,et al.  MAP kinase kinase kinase, MAP kinase kinase and MAP kinase. , 1994, Current opinion in genetics & development.

[82]  Pierre-Etienne Meunier,et al.  The non-cooperative tile assembly model is not intrinsically universal or capable of bounded Turing machine simulation , 2017, STOC.

[83]  Andrew Winslow,et al.  Verification in staged tile self-assembly , 2018, Natural Computing.

[84]  Jehoshua Bruck,et al.  Programmability of Chemical Reaction Networks , 2009, Algorithmic Bioprocesses.

[85]  Erik D. Demaine,et al.  One-dimensional staged self-assembly , 2012, Natural Computing.

[86]  Hao Yan,et al.  Functionalized DNA Nanostructures for Nanomedicine , 2013 .

[87]  Irving R. Epstein,et al.  An Introduction to Nonlinear Chemical Dynamics: Oscillations, Waves, Patterns, and Chaos , 1998 .

[88]  Teruo Fujii,et al.  Scaling down DNA circuits with competitive neural networks , 2013, Journal of The Royal Society Interface.

[89]  Ceren Kımna,et al.  Engineering an orchestrated release avalanche from hydrogels using DNA-nanotechnology. , 2019, Journal of controlled release : official journal of the Controlled Release Society.

[90]  Ho-Lin Chen,et al.  Active Self-Assembly of Simple Units Using an Insertion Primitive , 2013, SODA.

[91]  Andrei Voronkov,et al.  First-Order Theorem Proving and Vampire , 2013, CAV.

[92]  Hao Yan,et al.  DNA Origami with Complex Curvatures in Three-Dimensional Space , 2011, Science.

[93]  G. Seelig,et al.  Dynamic DNA nanotechnology using strand-displacement reactions. , 2011, Nature chemistry.

[94]  Erik Winfree,et al.  A General-Purpose CRN-to-DSD Compiler with Formal Verification, Optimization, and Simulation Capabilities , 2017, DNA.

[95]  N. Seeman Nucleic acid junctions and lattices. , 1982, Journal of theoretical biology.

[96]  Pieter Rein ten Wolde,et al.  Thermodynamics of Computational Copying in Biochemical Systems , 2015, 1503.00909.

[97]  Marta Kwiatkowska,et al.  Survey of fairness notions , 1989 .

[98]  Dana Randall Statistical Physics and Algorithms (Invited Talk) , 2020, STACS.

[99]  Luca Cardelli,et al.  The Cell Cycle Switch Computes Approximate Majority , 2012, Scientific Reports.

[100]  Andrew Winslow Staged self-assembly and polyomino context-free grammars , 2014, Natural Computing.

[101]  Ho-Lin Chen,et al.  A minimal requirement for self-assembly of lines in polylogarithmic time , 2018, Natural Computing.

[102]  J. Doye,et al.  Structural, mechanical, and thermodynamic properties of a coarse-grained DNA model. , 2010, The Journal of chemical physics.

[103]  Matthew Cook,et al.  Computation with finite stochastic chemical reaction networks , 2008, Natural Computing.

[104]  Jack H. Lutz,et al.  Strict self-assembly of discrete Sierpinski triangles , 2007, Theor. Comput. Sci..

[105]  G. Seelig,et al.  DNA as a universal substrate for chemical kinetics , 2010, Proceedings of the National Academy of Sciences.

[106]  Luvena L. Ong,et al.  Hierarchical Assembly of DNA Nanostructures Based on Four-Way Toehold-Mediated Strand Displacement. , 2018, Nano letters.

[107]  Erik D. Demaine,et al.  Know When to Fold 'Em: Self-Assembly of Shapes by Folding in Oritatami , 2018, DNA.

[108]  David J. Schwab,et al.  Landauer in the Age of Synthetic Biology: Energy Consumption and Information Processing in Biochemical Networks , 2015, bioRxiv.

[109]  Pekka Orponen,et al.  DNA rendering of polyhedral meshes at the nanoscale , 2015, Nature.

[110]  Tobias Nipkow,et al.  From LCF to Isabelle/HOL , 2019, Formal Aspects of Computing.

[111]  Christian Scheideler,et al.  Forming tile shapes with simple robots , 2018, Natural Computing.

[112]  G. Seelig,et al.  Enzyme-Free Nucleic Acid Logic Circuits , 2022 .

[113]  Adam H. Marblestone,et al.  Rapid prototyping of 3D DNA-origami shapes with caDNAno , 2009, Nucleic acids research.

[114]  Martin Feinberg,et al.  Foundations of Chemical Reaction Network Theory , 2019, Applied Mathematical Sciences.

[115]  Chrisantha Fernando,et al.  Turing Complete Catalytic Particle Computers , 2007, ECAL.

[116]  Juan Elezgaray,et al.  Connecting localized DNA strand displacement reactions. , 2015, Nanoscale.

[117]  J. Sweatt,et al.  The neuronal MAP kinase cascade: a biochemical signal integration system subserving synaptic plasticity and memory , 2001, Journal of neurochemistry.

[118]  Ho-Lin Chen,et al.  An Exponentially Growing Nubot System Without State Changes , 2019, UCNC.

[119]  David Furcy,et al.  New Bounds on the Tile Complexity of Thin Rectangles at Temperature-1 , 2018, DNA.

[120]  Ján Manuch,et al.  Simplifying Analyses of Chemical Reaction Networks for Approximate Majority , 2017, DNA.

[121]  Andrew Winslow,et al.  Nearly Constant Tile Complexity for any Shape in Two-Handed Tile Assembly , 2019, Algorithmica.

[122]  N. Seeman,et al.  Design and self-assembly of two-dimensional DNA crystals , 1998, Nature.

[123]  Ralph Johnson,et al.  design patterns elements of reusable object oriented software , 2019 .

[124]  Georg Seelig,et al.  A spatially localized architecture for fast and modular DNA computing. , 2017, Nature nanotechnology.

[125]  Dana Randall Phase Transitions and Emergent Phenomena in Random Structures and Algorithms (Keynote Talk) , 2017, DISC.

[126]  Erik D. Demaine,et al.  Programmable Assembly With Universally Foldable Strings (Moteins) , 2011, IEEE Transactions on Robotics.

[127]  Masami Hagiya,et al.  Implementation of Turing Machine Using DNA Strand Displacement , 2016, TPNC.

[128]  E. Elion,et al.  Ste5: a meeting place for MAP kinases and their associates. , 1995, Trends in cell biology.

[129]  Sebastián Uchitel,et al.  Less is More , 2016, ACM Trans. Softw. Eng. Methodol..

[130]  Luca Cardelli,et al.  Efficiency through uncertainty: scalable formal synthesis for stochastic hybrid systems , 2019, HSCC.

[131]  B. Bassler,et al.  Quorum sensing in bacteria. , 2001, Annual review of microbiology.

[132]  Hendrik Dietz,et al.  Building machines with DNA molecules , 2019, Nature Reviews Genetics.

[133]  Marta Z. Kwiatkowska,et al.  Probabilistic model checking of complex biological pathways , 2008, Theor. Comput. Sci..

[134]  M. Magnasco CHEMICAL KINETICS IS TURING UNIVERSAL , 1997 .

[135]  Ivan Viola,et al.  Adenita: Interactive 3D modeling and visualization of DNA Nanostructures , 2019, bioRxiv.

[136]  Joseph Sifakis,et al.  Model checking , 1996, Handbook of Automated Reasoning.

[137]  U. Alon An introduction to systems biology : design principles of biological circuits , 2019 .

[138]  Erik D. Demaine,et al.  Staged self-assembly: nanomanufacture of arbitrary shapes with O(1) glues , 2008, Natural Computing.

[139]  Andrew Winslow,et al.  Non-determinism Reduces Construction Time in Active Self-assembly Using an Insertion Primitive , 2018, COCOON.

[140]  Lulu Qian,et al.  Supporting Online Material Materials and Methods Figs. S1 to S6 Tables S1 to S4 References and Notes Scaling up Digital Circuit Computation with Dna Strand Displacement Cascades , 2022 .

[141]  Lulu Qian,et al.  A Simple DNA Gate Motif for Synthesizing Large-Scale Circuits , 2008, DNA.

[142]  Shinnosuke Seki,et al.  Programming Biomolecules That Fold Greedily During Transcription , 2016, MFCS.

[143]  Yan Liu,et al.  DNA-Templated Self-Assembly of Protein Arrays and Highly Conductive Nanowires , 2003, Science.

[144]  Ho-Lin Chen,et al.  Fast Algorithmic Self-assembly of Simple Shapes Using Random Agitation , 2014, DNA.

[145]  Luca Cardelli,et al.  Chemical reaction network designs for asynchronous logic circuits , 2016, Natural Computing.

[146]  S.-Y. Kuroda,et al.  Classes of Languages and Linear-Bounded Automata , 1964, Inf. Control..

[147]  Robert T. Schweller,et al.  Fuel Efficient Computation in Passive Self-Assembly , 2013, SODA.

[148]  C. Mao,et al.  DNA nanotechnology. , 2004, BioTechniques.

[149]  Sebastian Junges,et al.  Shepherding Hordes of Markov Chains , 2019, TACAS.

[150]  Andrew Winslow,et al.  Freezing Simulates Non-freezing Tile Automata , 2018, DNA.

[151]  Lulu Qian,et al.  Compiler-aided systematic construction of large-scale DNA strand displacement circuits using unpurified components , 2017, Nature Communications.

[152]  Cristopher Moore,et al.  The Nature of Computation , 2011 .

[153]  Hao Yan,et al.  DNA tile based self-assembly: building complex nanoarchitectures. , 2006, Chemphyschem : a European journal of chemical physics and physical chemistry.

[154]  M. Sahani,et al.  Algorithmic Self-Assembly of DNA , 2006 .

[155]  Xiaojun Ma,et al.  Synthesis of Tile Sets for DNA Self-Assembly , 2008, IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems.

[156]  Robert T. Schweller,et al.  Verification and Computation in Restricted Tile Automata , 2020, DNA.

[157]  Tomislav Plesa,et al.  Stochastic approximation of high-molecular by bi-molecular reactions , 2018, 1811.02766.

[158]  Zhenxin Wang,et al.  Towards multistep nanostructure synthesis: programmed enzymatic self-assembly of DNA/gold systems. , 2003, Angewandte Chemie.

[159]  Stephen Travis Pope,et al.  A cookbook for using the model-view controller user interface paradigm in Smalltalk-80 , 1988 .

[160]  A. Troisi,et al.  An agent-based approach for modeling molecular self-organization. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[161]  Matthew R. Lakin,et al.  A Logic Programming Language for Computational Nucleic Acid Devices. , 2018, ACS synthetic biology.

[162]  Xingsi Zhong,et al.  Fast arithmetic in algorithmic self-assembly , 2015, Natural Computing.

[163]  David Eisenstat,et al.  The computational power of population protocols , 2006, Distributed Computing.

[164]  Baoquan Ding,et al.  A DNA nanorobot functions as a cancer therapeutic in response to a molecular trigger in vivo , 2018, Nature Biotechnology.

[165]  Christel Baier,et al.  Principles of Model Checking (Representation and Mind Series) , 2008 .

[166]  Damien Woods,et al.  Parallel computation using active self-assembly , 2014, Natural Computing.

[167]  David Harel,et al.  Effective transformations on infinite trees, with applications to high undecidability, dominoes, and fairness , 1986, JACM.

[168]  Dana Randall,et al.  Phase Transitions in Random Dyadic Tilings and Rectangular Dissections , 2015, SODA.

[169]  Erik D. Demaine,et al.  Two Hands Are Better Than One (up to constant factors): Self-Assembly In The 2HAM vs. aTAM , 2013, STACS.