1 The Quest for Nanotechnology ................................. 1
Biotechnology and the Two-Week Revolution .................... 3
From Biotechnology to Bionanotechnology ...................... 4
What is Bionanotechnology? ................................... 6
2 Bionanomachines in Action .................................... 9
The Unfamiliar World of Bionanomachines ..................... 10
Gravity and inertia are negligible at the nanoscale ...... 10
Nanomachines show atomic granularity ..................... 11
Thermal motion is a significant force at the nanoscale ... 12
Bionanomachines require a water environment .............. 13
Modern Biomaterials ......................................... 14
Most natural bionanomachines are composed of protein ..... 15
Nucleic acids carry information .......................... 21
Lipids are used for infrastructure ....................... 24
Polysaccharides are used in specialized structural
roles .................................................... 27
The Legacy of Evolution ..................................... 28
Evolution has placed significant limitations on the
properties of natural biomolecules ....................... 31
Guided Tour of Natural Bionanomachinery ..................... 32
3 Biomolecular Design and Biotechnology ....................... 43
Recombinant DNA Technology .................................. 45
DNA may be engineered with commercially available enzymes ... 46
Site-directed mutagenesis makes specific changes in the
genome ...................................................... 52
Fusion proteins combine two functions .................... 52
Monoclonal Antibodies ....................................... 54
Biomolecular Structure Determination ........................ 57
X-ray crystallography provides atomic structures ......... 58
NMR spectroscopy may be used to derive atomic
structures ............................................... 61
Electron microscopy reveals molecular morphology ......... 62
Atomic force microscopy probes the surface of
biomolecules ............................................. 64
Molecular Modeling .......................................... 66
Bionanomachines are visualized with computer graphics .... 67
Computer modeling is used to predict biomolecular ........ 68
Structure and function
The protein folding problem .............................. 69
Docking simulations predict the modes of biomolecular
interaction .............................................. 72
New functionalities are developed with computer-
assisted molecular design ................................ 74
4 Structural Principles of Bionanotechnology .................. 75
Natural Bionanomachinery is Designed for a Specific ......... 76
Environment
A Hierarchical Strategy Allows Construction of
Nanomachines ................................................ 77
The Raw Materials: Biomolecular Structure and Stability ..... 80
Molecules are composed of atoms linked by covalent
bonds .................................................... 80
Dispersion and repulsion forces act at close range ....... 84
Hydrogen bonds provide stability and specificity ......... 86
Electrostatic interactions are formed between charged
atoms .................................................... 87
The hydrophobic effect stabilizes biomolecules in water .. 89
Protein Folding ............................................. 91
Not all protein sequences adopt stable structures ........ 93
Globular proteins have a hierarchical structure .......... 93
Stable globular structure requires a combination of
design strategies ........................................ 95
Chaperones provide the optimal environment for folding ... 98
Rigidity can make proteins more stable at high
temperatures ............................................ 100
Many proteins make use of disorder ...................... 101
Self-Assembly .............................................. 103
Symmetry allows self-assembly of stable complexes with
defined size ............................................ 105
Quasisymmetry is used to build assemblies too large for
perfect symmetry ........................................ 113
Crowded conditions promote self-assembly ................ 115
Self-Organization .......................................... 116
Lipids self-organize into bilayers ...................... 117
Lipid bilayers are fluid ................................ 118
Proteins may be designed to self-organize with lipid
bilayers ................................................ 119
Molecular Recognition ...................................... 121
Crane principles for molecular recognition .............. 122
Atomicity limits the tolerance of combining sites ....... 127
Flexibility ................................................ 129
Biomolecules show flexibility at all levels ............. 130
Flexibility poses great challenges for the design of
bionanomachines ......................................... 134
5 Functional Principles of Bionanotechnology ................. 135
Information-Driven Nanoassembly ............................ 136
Nucleic acids carry genetic information ................. 136
Ribosomes construct proteins ............................ 140
Information is stored in very compact form .............. 142
Energetics ................................................. 145
Chemical energy is transferred by carrier molecules ..... 146
Light is captured with specialized small molecules ...... 149
Protein pathways transfer single electrons .............. 151
Electrical conduction and charge transfer have been
observed in DNA ......................................... 155
Electrochemical gradients are created across membranes .. 156
Chemical Transformation .................................... 158
Enzymes reduce the entropy of a chemical reaction ....... 162
Enzymes create environments that stabilize transition
states .................................................. 163
Enzymes use chemical tools to perform a reaction ........ 164
Regulation ................................................. 167
Protein activity may be regulated through allosteric
motions ................................................. 167
Protein action may be regulated by covalent
modification ............................................ 171
Biomaterials ............................................... 173
Helical assembly of subunits forms filaments and
fibrils ................................................. 174
Microscale infrastructure is built from fibrous
components .............................................. 177
Minerals are combined with biomaterials for special
applications ............................................ 181
Elastic proteins use disordered chains .................. 184
Cells make specific and general adhesives ............... 187
Biomolecular Motors ........................................ 189
ATP powers linear motors ................................ 190
ATP synthase and flagellar motors are rotary motors ..... 194
Brownian ratchets rectify random thermal motions ........ 201
Traffic Across Membranes ................................... 203
Potassium channels use a selectivity filter ............. 205
ABC transporters use a flip-flop mechanism .............. 207
Bacteriorhodopsin uses light to pump protons ............ 207
Biomolecular Sensing ....................................... 211
Smell and taste detect specific molecules ............... 212
Light is sensed by monitoring light-sensitive motions
in retinal .............................................. 213
Mechanosensory receptors sense motion across
a membrane .............................................. 213
Bacteria sense chemical gradients by rectification of
random motion ........................................... 216
Self-Replication ........................................... 216
Cells are autonomous self-replicators ................... 217
The basic design of cells is shaped by the processes
of evolution ............................................ 220
Machine-Phase Bionanotechnology ............................ 221
Muscle sarcomeres ....................................... 221
Nerves .................................................. 224
6 Bionanotechnology Today .................................... 227
Basic Capabilities ......................................... 228
Natural proteins may be simplified ...................... 228
Proteins are being designed from scratch ................ 230
Proteins may be constructed with nonnatural amino
acids ................................................... 232
Peptide nucleic acids provide a stable alternative to
DNA and RNA ............................................. 235
Nanomedicine Today ......................................... 237
Computer-aided drug design has produced effective
anti-AIDS drugs ......................................... 238
Immunotoxins are targeted cell killers .................. 240
Drugs may be delivered with liposomes ................... 241
Artificial blood saves lives ............................ 243
Gene therapy will correct genetic defects ............... 245
General medicine is changing into personalized
medicine ................................................ 247
Self-Assembly at Many Scales ............................... 248
Self-assembling DNA scaffolds have been constructed ..... 248
Cyclic peptides form nanotubes .......................... 250
Fusion proteins self-assemble into extended structures .. 252
Small organic molecules self-assemble into large
structures .............................................. 252
Larger objects may be self-assembled .................... 254
Harnessing Molecular Motors ................................ 257
ATP synthase is used as a rotary motor .................. 257
Molecular machines have been built of DNA ............... 259
DNA Computers .............................................. 261
The first DNA computer solved a traveling salesman
problem .................................................... 262
Satisfiability problems are solved by DNA computing ..... 264
A Turing machine has been built with DNA ................ 265
Molecular Design Using Biological Selection ................ 266
Antibodies may be turned into enzymes ................... 267
Peptides may be screened with bacteriophage display
libraries ............................................... 271
Nucleic acids with novel functions may be selected ...... 273
Functional bionanomachines are surprisingly common ...... 277
Artificial Life ............................................ 277
Artificial protocells reproduce by budding .............. 278
Self-replicating molecules are an elusive goal .......... 280
ATP is made with an artificial photosynthetic liposome .. 281
Poliovirus has been created with only a genetic
blueprint ............................................... 283
Hybrid Materials ........................................... 285
Nanoscale conductive metal wires may be constructed
with DNA ................................................... 285
Patterned aggregates of gold nanoparticles are formed
with DNA ................................................ 286
DNA flexes a sensitive mechanical lever ................. 287
Researchers are harnessing biomineralization ............ 288
Biosensors ................................................. 290
Antibodies are widely used as biosensors ................ 291
Biosensors detect glucose levels for management of
diabetes ................................................ 292
Engineered nanopores detect specific DNA sequences ...... 294
7 The Future of Bionanotechnology ............................ 295
A Timetable for Bionanotechnology .......................... 296
Lessons for Molecular Nanotechnology ....................... 298
Three Case Studies ......................................... 300
Case study: Nanotube synthase ........................... 301
Case study: A general nanoscale assembler ............... 303
Case study: Nanosurveillance ............................ 305
Ethical Considerations ..................................... 309
Respect for life ........................................ 309
Potential dangers ....................................... 310
Final thoughts .......................................... 311
Literature .................................................... 313
Sources ....................................................... 320
Index ......................................................... 323
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