Developmental Self-Assembly of a DNA Tetrahedron

Kinetically controlled isothermal growth is fundamental to biological development, yet it remains challenging to rationally design molecular systems that self-assemble isothermally into complex geometries via prescribed assembly and disassembly pathways. By exploiting the programmable chemistry of base pairing, sophisticated spatial and temporal control have been demonstrated in DNA self-assembly, but largely as separate pursuits. By integrating temporal with spatial control, here we demonstrate the “developmental” self-assembly of a DNA tetrahedron, where a prescriptive molecular program orchestrates the kinetic pathways by which DNA molecules isothermally self-assemble into a well-defined three-dimensional wireframe geometry. In this reaction, nine DNA reactants initially coexist metastably, but upon catalysis by a DNA initiator molecule, navigate 24 individually characterizable intermediate states via prescribed assembly pathways, organized both in series and in parallel, to arrive at the tetrahedral final product. In contrast to previous work on dynamic DNA nanotechnology, this developmental program coordinates growth of ringed substructures into a three-dimensional wireframe superstructure, taking a step toward the goal of kinetically controlled isothermal growth of complex three-dimensional geometries.

[1]  Mudalige Thilak Kumara,et al.  Assembly pathway analysis of DNA nanostructures and the construction of parallel motifs. , 2008, Nano letters.

[2]  T. G. Martin,et al.  Rapid Folding of DNA into Nanoscale Shapes at Constant Temperature , 2012, Science.

[3]  E. Winfree,et al.  Algorithmic Self-Assembly of DNA Sierpinski Triangles , 2004, PLoS biology.

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

[5]  Chenxiang Lin,et al.  Knitting Complex Weaves with Dna Origami This Review Comes from a Themed Issue on Nucleic Acids Edited Dna and the Biosynthetic Advantage Single-layer Dna Origami Multi-layer Dna Origami Scaling to Greater Complexity Conclusions and Future Outlook , 2022 .

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

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

[8]  Self-assembly of two-dimensional DNA crystals , 2004 .

[9]  J. Reif,et al.  A unidirectional DNA walker that moves autonomously along a track. , 2004, Angewandte Chemie.

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

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

[12]  N. Seeman,et al.  A robust DNA mechanical device controlled by hybridization topology , 2002, Nature.

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

[14]  William M. Shih,et al.  A 1.7-kilobase single-stranded DNA that folds into a nanoscale octahedron , 2004, Nature.

[15]  N. Seeman.  DNA in a material world , 2003, Nature.

[16]  A. Turberfield,et al.  A DNA-fuelled molecular machine made of DNA , 2022 .

[17]  P. Yin,et al.  Complex shapes self-assembled from single-stranded DNA tiles , 2012, Nature.

[18]  E. Winfree,et al.  Synthesis of crystals with a programmable kinetic barrier to nucleation , 2007, Proceedings of the National Academy of Sciences.

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

[20]  C. Mao,et al.  Hierarchical self-assembly of DNA into symmetric supramolecular polyhedra , 2008, Nature.

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

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

[23]  Russell P. Goodman,et al.  Rapid Chiral Assembly of Rigid DNA Building Blocks for Molecular Nanofabrication , 2005, Science.

[24]  N. Seeman,et al.  A precisely controlled DNA biped walking device , 2004 .

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

[26]  David R. Liu,et al.  Ordered multistep synthesis in a single solution directed by DNA templates. , 2005, Angewandte Chemie.

[27]  David Yu Zhang,et al.  Cooperative hybridization of oligonucleotides. , 2011, Journal of the American Chemical Society.

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

[29]  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 .

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

[31]  Pamela E. Constantinou,et al.  From Molecular to Macroscopic via the Rational Design of a Self-Assembled 3D DNA Crystal , 2009, Nature.

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

[33]  Matt A. King,et al.  Three-Dimensional Structures Self-Assembled from DNA Bricks , 2012 .

[34]  Robert M. Dirks,et al.  Triggered amplification by hybridization chain reaction. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[35]  N. Seeman,et al.  Synthesis from DNA of a molecule with the connectivity of a cube , 1991, Nature.

[36]  C. Mao,et al.  Tensegrity: construction of rigid DNA triangles with flexible four-arm DNA junctions. , 2004, Journal of the American Chemical Society.

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

[38]  Ruojie Sha,et al.  A Bipedal DNA Brownian Motor with Coordinated Legs , 2009, Science.

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

[40]  Hao Yan,et al.  DNA Gridiron Nanostructures Based on Four-Arm Junctions , 2013, Science.

[41]  A. Turberfield,et al.  DNA nanomachines. , 2007, Nature nanotechnology.

[42]  Harry M. T. Choi,et al.  Programming DNA Tube Circumferences , 2008, Science.

[43]  J. Reif,et al.  Directed nucleation assembly of DNA tile complexes for barcode-patterned lattices , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[44]  David Yu Zhang,et al.  Towards Domain-Based Sequence Design for DNA Strand Displacement Reactions , 2010, DNA.

[45]  Erik Winfree,et al.  An information-bearing seed for nucleating algorithmic self-assembly , 2009, Proceedings of the National Academy of Sciences.

[46]  N. Pierce,et al.  A synthetic DNA walker for molecular transport. , 2004, Journal of the American Chemical Society.