DNA Nanoscience

Kenneth Douglas is a member of the Research Faculty in the Department of Physics at the University of Colorado-Boulder. He received his B.A. (mathematics) and M.S. (physics) at the University of Chicago and his Ph.D. (physics) at the University of Colorado-Boulder. His area of specialization is biomimetic nanofabrication. He devised a strategy that employs the surface layers of bacterial extremophiles — e.g., Sulfolobus acidocaldarius — as masks to fabricate nanoscale periodic patterns on inorganic substrates. He is co-inventor of the first-ever U.S. patents for parallel fabrication of nanoscale multi-device structures. His work has appeared in Science, Nature, Biophysical Journal, Applied Physics Letters, Physical Review B, Surface Science, FEMS Microbiology Reviews, Journal of Applied Physics, Popular Science and elsewhere. Douglas has authored multiple book chapters and seven U.S. patents.

• A Note to the ReaderPrefaceAuthor BiographyAcknowledgmentsINTRODUCTION: Grandma Needs a WalkerPART I — The Story Line and Its UnderpinningsCHAPTER ONE — Down the Road and the GemischDramatis Personae, Part I: Nadrian SeemanMolecular Crystals—Inspiration from EscherPerspiration and ReinventionDramatis Personae, Part II: Noel Clark, Tommaso BelliniLiquid Crystals and Self-AssemblySeeman, Bellini and Clark, and Base ComplementarityConventional Wisdom and an Alternative ViewEndnotesCHAPTER TWO — DNA: The Molecule That Makes Life Work—and MoreErwin ChargaffRosalind FranklinJames Watson, Francis Crick, and Maurice WilkinsDNA SequencingPolyacrylamide Gel Electrophoresis (PAGE)DNA SynthesisExercises for Chapter TwoEndnotesCHAPTER THREE — Travels to the NanoworldThe Scanning Tunneling Microscope (STM)Moving Atoms With an STMStanding WavesQuantum CorralsNanomethodologySpherical Nucleic Acids (SNAs)Biodiagnostic Detection Using SNAsExercises for Chapter ThreeEndnotesCHAPTER FOUR—Liquid Crystals: Nature’s Delicate Phase of MatterPhase TransitionsClasses of Liquid CrystalsCell Membranes and the Langmuir TroughMicellesLiquid Crystal DisplaysExercises for Chapter FourEndnotesCHAPTER FIVE — Tools of the TradePolarized Light MicroscopyLiquid Crystal Texture Seen Through a Depolarized Light MicroscopeTransmission Electron Microscopy (TEM)Atomic Force Microscopy (AFM)X-Ray Diffraction and Bragg’s LawThe Phase ProblemSynchrotron X-Ray DiffractionExercises for Chapter FiveEndnotesPART II — The Emerging Technology: Nanomaterials Constructed From DNACHAPTER SIX — The Three Pillars of Structural DNA NanotechnologyBranched DNA and DNA JunctionsSticky EndsImmobile Four-Arm DNA JunctionTwo-Dimensional Ligation of DNA JunctionsDeconstruction of Concatenated Nucleic Acid JunctionsMacrocyclesThree-Dimensional Constructions and CatenanesThe DNA CubeExercises for Chapter SixEndnotesCHAPTER SEVEN — Motif Generation, Sequence Design, Nanomechanical DevicesFlexible Junctions ReduxThe Double-Crossover (DX) MoleculeDesign and Self-Assembly of Two-Dimensional DNA CrystalsTwo-Dimensional Nanoparticle ArraysSequence DesignNanomechanical DevicesExercises for Chapter SevenEndnotesCHAPTER EIGHT—DNA Origami, DNA BricksScaffolded DNA OrigamiDNA Origami PatternsStrand Invasion also called Strand DisplacementDNA Origami With Complex Curvatures in Three DimensionsDNA Tiles in Two DimensionsDNA Bricks in Three DimensionsDNA Brick Shapes in Three DimensionsDNA Brick CrystalsSeeman, Rothemund, and YinExercises for Chapter EightEndnotesCHAPTER NINE — DNA Assembly Line and the Triumph of Tensegrity TrianglesDNA Nanoscale Assembly Line (Overview)DNA WalkersDNA Machines and Paranemic Crossover MoleculesDNA Cassette With Robot Arm and DNA Origami TrackDNA Assembly LineThe Triumph of Tensegrity TrianglesExercises for Chapter NineEndnotesBRIEF INTERLUDE I — Back to MethuselahMolecular-Scale WeavingMoors and Crossover MoleculesTensegrity SculptingMayan Pottery, Chirality, and the Handedness of LifeEndnotesCHAPTER TEN — DNA Nanotechnology Meets the Real WorldCell Membrane ChannelsSynthetic Membrane Channels via DNA NanotechnologyCurrent GatingChannels as Single-Molecule SensorsMolecular Nanorobots Built by DNA Origami: Cell-Targeted Drug DeliveryTests of Nanorobot FunctionTest of Binding Discrimination: Healthy Cells vs. Leukemia Cells (NK Cells)Exercises for Chapter TenEndnotesPART III — The Possible Origins of Life’s Information CarrierCHAPTER ELEVEN — Chance FindingsOnsager’s Criterion for an Isotropic-Nematic Liquid Crystal Phase TransitionNanoDNA Seems to Violate Onsager’s Venerable CriterionThe DetailsShifting GearsPhase Separation into Liquid Crystal DropletsThe Depletion InteractionFlory’s ModelExercises for Chapter ElevenEndnotesCHAPTER TWELVE — Unexpected ConsequencesHierarchical Self-AssemblyNanoRNABlunt Ends and Sticky EndsBase Stacking ForcesThe Scope of the Self-Assembly Mechanisms of Nucleic AcidsRandom-Sequence NanoDNAThe Strange World of Random-Sequence NanoDNALiquid Crystal Ordering of Random-Sequence NanoDNANon-Equilibrium Statistical Mechanics: Kinetic Arrest and Nonergodic BehaviorExercises for Chapter TwelveEndnotesCHAPTER THIRTEEN — Ligation: Blest be the Tie That BindsNanoDNA Stacking: Weak Physical Attractive Forces vs. Chemical LigationAbiotic Ligation Experiments with EDCThe Scheme: Polyethylene glycol (PEG)-Induced Phase SeparationGel Electrophoresis of D1p Oligomers With Polyacrylamide and Agarose GelsAnother Stellar Contribution by Chemist Paul J. FloryAnalysis of Gel Profiles: The Experimental Data is Well Described by the Flory ModelThe Lowdown on Ligation EfficiencyThe Liquid Crystal Phase as GatekeeperCascaded Phase SeparationExercises for Chapter ThirteenEndnotesBRIEF INTERLUDE II — The Handedness of LifeChiralityLife is HomochiralMacroscopic Chiral Helical Precession of Molecular OrientationBellini and Clark Examine NanoDNA ChiralityA Lighter Take on ChiralityExercises for Brief Interlude IIEndnotesCHAPTER FOURTEEN — All the World’s a Stage and Life’s a Play—Did it Arise From Clay?Emergence and ComplexityMiller-Urey ExperimentRNA World HypothesisOther Plausible VenuesReplicator-First vs. Metabolism-FirstFeats of ClayThe Lipid WorldLiquid Crystals in the Work of Deamer and the Work of Bellini/ClarkManfred Eigen and Stuart KauffmanExercises for Chapter FourteenEndnotesCHAPTER FIFTEEN — The Passover Question: Why is This Origins Proposal Different From All Other Proposals?Emergence and Broken SymmetryAbout-FaceOccam’s RazorThe RNA World RevisitedSticky Business, Part I: What Constitutes Plausible Prebiotic Conditions?Sticky Business, Part II: The Origins Question—Whose Home Turf Is It?Discovering the Physical Processes that Enabled the Chemistry of LifeMetabolism-First RevisitedComputer Simulations and Mathematical ModelingAn Ancient "Liquid Crystal World"EndnotesEpilogueAPPENDIX — Texture of Liquid Crystal Optical ImagesSmectic Phase Liquid Crystal TextureBent-Core MoleculesExtinction BrushesChiral Nematic Texture of NanoDNA Liquid CrystalsColumnar Texture of NanoDNA Liquid CrystalsEndnotesGlossaryIndex

‘DNA Nanoscience takes us on a journey into the future, where sub-microscopic gadgets built from DNA may be used to detect specific molecules one-at-a-time or to deliver therapeutic drugs specifically to cancer cells. Looking in the other direction, the journey takes us back 4 billion years to a time when the self-organization of DNA into liquid crystals may have facilitated the reproduction of what would become our genetic material, arguably the key step in the origin of life.DNA Nanoscience is scholarly and full of technical figures. But the science is accompanied by clear explanations that make it accessible to college student and science-savvy citizens. It is a pleasure to find a book that is so true to the science while being so enjoyable to read.’– Thomas R. CechDistinguished Professor, University of Colorado-Boulder; Director, BioFrontiers Institute; Nobel Laureate (Chemistry 1989).‘Douglas’ DNA Nanoscience is something of a miracle.’– Stuart KauffmanEmeritus Professor Biochemistry and Biophysics, University of Pennsylvania; Affiliate Professor, The Institute for Systems Biology, Seattle; Author of At Home in the Universe.‘This book changed my life. Every seven years, as my sabbatical approaches, I search about for a new direction to focus my research and Ken Douglas’ book, DNA Nanoscience, appeared just in time.’– Seth FradenProfessor of Physics; Director, The Bioinspired Soft Materials Center, Brandeis University.‘Instructive like a textbook and exciting like a novel! For everybody interested in modern natural sciences, this book is a must to read.’– Andreas HerrmannProfessor of Polymer Chemistry and Bioengineering; Chair of the Board, The Zernike Institute for Advanced Materials; University of Groningen, The Netherlands.‘To sum up, this is both a lively and profound book, the reading of which I strongly recommend.’– Jacques ProstDirector Emeritus of CNRS (Le Centre national de la recherche scientifique) at Institut Curie, Paris; Distinguished Professor, National University of Singapore.‘This book tells a fascinating new story about DNA. The subject matter also stretches as needed into biology to teach basic ideas about cell membranes and metabolism. It provides a wonderful taste of DNA nanoscience at the research frontier.’– Arjun G. YodhJames M. Skinner Professor of Science, Endowed Chair; Director, PENN Laboratory for Research on the Structure of Matter, University of Pennsylvania.‘The only way that the general public will continue to trust the proclamation of the scientific establishment is through books like this one – where the foibles and fears and eccentricities of the scientists are shown to be the same as those of the artist, musician and businessman. Scientists are just artists who want to work with mother nature, without the freedom to make up new worlds as we go along. The real world is magical enough for them.’– Joseph A. Zasadzinski3M Harry Heltzer Chair in Multidisciplinary Science and Technology; Chemical Engineering and Materials Science, University of Minnesota.'The book’s eclectic and elaborate vision, looking back to the ancient past and forward to the equally unknowable future sets Douglas’ DNA Nanoscience apart from other attempts to present DNA nanoscience.... Written in beautiful prose and richly illustrated with over 200 full-color figures ... it also serves as a bird’s-eye survey for a more general readership, viz., for those in the public who are curious and enjoy thinking. These citizens are aware of DNA nanoscience snippets making it into the daily news but would like to acquire a deeper, more meaningful and thorough understanding of what the fuss is all about.Douglas’ book DNA Nanoscience: From Prebiotic Origins to Emerging Nanotechnology covers an astoundingly broad ground.... By writing this book on the emerging field of DNA nanoscience Kenneth Douglas has thus done a double service—to science as well as to its public image. I believe that the reception of the book will do justice to the meticulous research and artistry of this tome.'– Rudolf Podgornik (Jožef Stefan Institute)Journal of Biological Physics (August 2016), DOI: 10.1007/s10867-016-9425-4.