DNA Nanoscience: From Prebiotic Origins to Emerging Nanotechnology, 1st Edition (Paperback) book cover

DNA Nanoscience

From Prebiotic Origins to Emerging Nanotechnology, 1st Edition

By Kenneth Douglas

CRC Press

424 pages | 207 Color Illus.

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pub: 2016-08-15
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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.


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.

Table of Contents

A Note to the Reader


Author Biography


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

Erwin Chargaff

Rosalind Franklin

James Watson, Francis Crick, and Maurice Wilkins

DNA Sequencing

Polyacrylamide Gel Electrophoresis (PAGE)

DNA Synthesis

Exercises for Chapter Two


CHAPTER THREE — Travels to the Nanoworld

The Scanning Tunneling Microscope (STM)

Moving Atoms With an STM

Standing Waves

Quantum Corrals


Spherical Nucleic Acids (SNAs)

Biodiagnostic Detection Using SNAs

Exercises for Chapter Three


CHAPTER FOUR — Liquid Crystals: Nature’s Delicate Phase of Matter

Phase Transitions

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

Sticky Ends

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

Sequence Design

Nanomechanical Devices

Exercises for Chapter Seven



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 Walkers

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

Molecular-Scale Weaving

Moors and Crossover Molecules

Tensegrity Sculpting

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

Current Gating

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

The Details

Shifting Gears

Phase Separation into Liquid Crystal Droplets

The Depletion Interaction

Flory’s Model

Exercises for Chapter Eleven


CHAPTER TWELVE — Unexpected Consequences

Hierarchical Self-Assembly


Blunt Ends and Sticky Ends

Base Stacking Forces

The Scope of the Self-Assembly Mechanisms of Nucleic Acids

Random-Sequence NanoDNA

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

Miller-Urey Experiment

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


Occam’s Razor

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

Metabolism-First Revisited

Computer Simulations and Mathematical Modeling

An Ancient "Liquid Crystal World"



APPENDIX — Texture of Liquid Crystal Optical Images

Smectic Phase Liquid Crystal Texture

Bent-Core Molecules

Extinction Brushes

Chiral Nematic Texture of NanoDNA Liquid Crystals

Columnar Texture of NanoDNA Liquid Crystals




About the Author

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.

Subject Categories

BISAC Subject Codes/Headings:
MEDICAL / Biochemistry
SCIENCE / Biotechnology