DNA Nanoscience: From Prebiotic Origins to Emerging Nanotechnology melds two tales of DNA. One is a look at the first 35 years of DNA nanotechnology to better appreciate what lies ahead in this emerging field. The other story looks back 4 billion years to the possible origins of DNA which are shrouded in mystery. The book is divided into three parts comprised of 15 chapters and two Brief Interludes.
Part I includes subjects underpinning the book such as a primer on DNA, the broader discipline of nanoscience, and experimental tools used by the principals in the narrative. Part II examines the field of structural DNA nanotechnology, founded by biochemist/crystallographer Nadrian Seeman, that uses DNA as a construction material for nanoscale structures and devices, rather than as a genetic material. Part III looks at the work of physicists Noel Clark and Tommaso Bellini who found that short DNA (nanoDNA) forms liquid crystals that act as a structural gatekeeper, orchestrating a series of self-assembly processes using nanoDNA. This led to an explanation of the polymeric structure of DNA and of how life may have emerged from the prebiotic clutter.
Table of Contents
A Note to the Reader
INTRODUCTION — Grandma Needs a Walker
PART I — The Story Line and Its Underpinnings
CHAPTER ONE — Down the Road and the Gemisch
Dramatis Personae, Part I: Nadrian Seeman
Molecular Crystals — Inspiration from Escher
Perspiration and Reinvention
Dramatis Personae, Part II: Noel Clark, Tommaso Bellini
Liquid Crystals and Self-Assembly
Seeman, Bellini and Clark, and Base Complementarity
Conventional Wisdom and an Alternative View
CHAPTER TWO — DNA: The Molecule That Makes Life Work—and More
James Watson, Francis Crick, and Maurice Wilkins
Polyacrylamide Gel Electrophoresis (PAGE)
Exercises for Chapter Two
CHAPTER THREE — Travels to the Nanoworld
The Scanning Tunneling Microscope (STM)
Moving Atoms With an STM
Spherical Nucleic Acids (SNAs)
Biodiagnostic Detection Using SNAs
Exercises for Chapter Three
CHAPTER FOUR — Liquid Crystals: Nature’s Delicate Phase of Matter
Classes of Liquid Crystals
Cell Membranes and the Langmuir Trough
Liquid Crystal Displays
Exercises for Chapter Four
CHAPTER FIVE — Tools of the Trade
Polarized Light Microscopy
Liquid Crystal Texture Seen Through a Depolarized Light Microscope
Transmission Electron Microscopy (TEM)
Atomic Force Microscopy (AFM)
X-Ray Diffraction and Bragg’s Law
The Phase Problem
Synchrotron X-Ray Diffraction
Exercises for Chapter Five
PART II — The Emerging Technology: Nanomaterials Constructed From DNA
CHAPTER SIX — The Three Pillars of Structural DNA Nanotechnology
Branched DNA and DNA Junctions
Immobile Four-Arm DNA Junction
Two-Dimensional Ligation of DNA Junctions
Deconstruction of Concatenated Nucleic Acid Junctions
Three-Dimensional Constructions and Catenanes
The DNA Cube
Exercises for Chapter Six
CHAPTER SEVEN — Motif Generation, Sequence Design, Nanomechanical Devices
Flexible Junctions Redux
The Double-Crossover (DX) Molecule
Design and Self-Assembly of Two-Dimensional DNA Crystals
Two-Dimensional Nanoparticle Arrays
Exercises for Chapter Seven
CHAPTER EIGHT — DNA Origami, DNA Bricks
Scaffolded DNA Origami
DNA Origami Patterns
Strand Invasion also called Strand Displacement
DNA Origami With Complex Curvatures in Three Dimensions
DNA Tiles in Two Dimensions
DNA Bricks in Three Dimensions
DNA Brick Shapes in Three Dimensions
DNA Brick Crystals
Seeman, Rothemund, and Yin
Exercises for Chapter Eight
CHAPTER NINE — DNA Assembly Line and the Triumph of Tensegrity Triangles
DNA Nanoscale Assembly Line (Overview)
DNA Machines and Paranemic Crossover Molecules
DNA Cassette With Robot Arm and DNA Origami Track
DNA Assembly Line
The Triumph of Tensegrity Triangles
Exercises for Chapter Nine
BRIEF INTERLUDE I — Back to Methuselah
Moors and Crossover Molecules
Mayan Pottery, Chirality, and the Handedness of Life
CHAPTER TEN — DNA Nanotechnology Meets the Real World
Cell Membrane Channels
Synthetic Membrane Channels via DNA Nanotechnology
Channels as Single-Molecule Sensors
Molecular Nanorobots Built by DNA Origami: Cell-Targeted Drug Delivery
Tests of Nanorobot Function
Test of Binding Discrimination: Healthy Cells vs. Leukemia Cells (NK Cells)
Exercises for Chapter Ten
PART III — The Possible Origins of Life’s Information Carrier
CHAPTER ELEVEN — Chance Findings
Onsager’s Criterion for an Isotropic-Nematic Liquid Crystal Phase Transition
NanoDNA Seems to Violate Onsager’s Venerable Criterion
Phase Separation into Liquid Crystal Droplets
The Depletion Interaction
Exercises for Chapter Eleven
CHAPTER TWELVE — Unexpected Consequences
Blunt Ends and Sticky Ends
Base Stacking Forces
The Scope of the Self-Assembly Mechanisms of Nucleic Acids
The Strange World of Random-Sequence NanoDNA
Liquid Crystal Ordering of Random-Sequence NanoDNA
Non-Equilibrium Statistical Mechanics: Kinetic Arrest and Nonergodic Behavior
Exercises for Chapter Twelve
CHAPTER THIRTEEN — Ligation: Blest be the Tie That Binds
NanoDNA Stacking: Weak Physical Attractive Forces vs. Chemical Ligation
Abiotic Ligation Experiments with EDC
The Scheme: Polyethylene glycol (PEG)-Induced Phase Separation
Gel Electrophoresis of D1p Oligomers With Polyacrylamide and Agarose Gels
Another Stellar Contribution by Chemist Paul J. Flory
Analysis of Gel Profiles: The Experimental Data is Well Described by the Flory Model
The Lowdown on Ligation Efficiency
The Liquid Crystal Phase as Gatekeeper
Cascaded Phase Separation
Exercises for Chapter Thirteen
BRIEF INTERLUDE II — The Handedness of Life
Life is Homochiral
Macroscopic Chiral Helical Precession of Molecular Orientation
Bellini and Clark Examine NanoDNA Chirality
A Lighter Take on Chirality
Exercises for Brief Interlude II
CHAPTER FOURTEEN — All the World’s a Stage and Life’s a Play—Did it Arise From Clay?
Emergence and Complexity
RNA World Hypothesis
Other Plausible Venues
Replicator-First vs. Metabolism-First
Feats of Clay
The Lipid World
Liquid Crystals in the Work of Deamer and the Work of Bellini/Clark
Manfred Eigen and Stuart Kauffman
Exercises for Chapter Fourteen
CHAPTER FIFTEEN — The Passover Question: Why is This Origins Proposal Different From All Other Proposals?
Emergence and Broken Symmetry
The RNA World Revisited
Sticky 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 Life
Computer Simulations and Mathematical Modeling
An Ancient "Liquid Crystal World"
APPENDIX — Texture of Liquid Crystal Optical Images
Smectic Phase Liquid Crystal Texture
Chiral Nematic Texture of NanoDNA Liquid Crystals
Columnar Texture of NanoDNA Liquid Crystals
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.
‘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. Cech
Distinguished Professor, University of Colorado-Boulder; Director, BioFrontiers Institute; Nobel Laureate (Chemistry 1989).
‘Douglas’ DNA Nanoscience is something of a miracle.’
– Stuart Kauffman
Emeritus 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 Fraden
Professor 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 Herrmann
Professor 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 Prost
Director 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. Yodh
James 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. Zasadzinski
3M 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.
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