Chapter 1. The Quest for Nanotechnology

            Biotechnology and the Two-Week Revolution

            From Biotechnology to Bionanotechnology

            What is Bionanotechnology?


Chapter 2. Bionanomachines in Action

            The Unfamiliar World of Bionanomachines

                        Gravity and inertia are negligible at the nanoscale

                        Nanomachines show atomic granularity

                        Thermal motion is a significant force at the nanoscale

                        Bionanomachines require a water environment

            Modern Biomaterials

                        Most natural bionanomachines are composed of protein

                        Nucleic acids carry information

                        Lipids are used for infrastructure

                        Polysaccharides are used in specialized structural roles

            Guided Tour of Natural Bionanomachinery

            The Legacy of Evolution

                        Evolution has placed significant limitations on the properties

of natural biomolecules


Chapter 3. Biomolecular Design and Biotechnology

            Recombinant DNA Technology

                        DNA may be engineered with commercially available enzymes

                        Site-directed mutagenesis makes specific changes in the genome

                        Fusion proteins combine two functions

            Monoclonal Antibodies

            Biomolecular Structure Determination

                        X-ray crystallography provides atomic structures

                        NMR spectroscopy may be used to derive atomic structures

                        Electron microscopy reveals molecular morphology

                        Atomic force microscopy probes the surface of biomolecules

            Molecular Modelling

                        Bionanomachines are visualized using computer graphics

                        Computer modelling is used to predict biomolecular structure and function

                        The protein folding problem

                        Docking simulations predict the modes of biomolecular interaction

                        New functionalities are developed using computer-assisted

 molecular design


Chapter 4. Structural Principles of Bionanotechnology

                        Natural bionanomachinery is designed for a specific environment

                        A hierarchical strategy allows construction of nanomachines

            The Raw Materials: Biomolecular Structure and Stability

                        Molecules are composed of atoms linked by covalent bonds

                        Dispersion and repulsion forces act at close range

                        Hydrogen bonds provide stability and specificity

                        Electrostatic interactions are formed between charged atoms

                        The hydrophobic effect stabilizes biomolecules in water

            Protein Folding

                        Not all protein sequences adopt stable structures

                        Globular proteins have a hierarchical structure

                        Stable globular structure requires a combination of design strategies

                        Chaperones provide the optimal environment for folding

                        Rigidity can make proteins more stable at high temperatures

                        Many proteins make use of disorder


                        Symmetry allows self-assembly of stable complexes with defined size

                        Quasisymmetry is used to build assemblies too large for perfect symmetry

                        Crowded conditions promote self-assembly


                        Lipids self-organize into bilayers

                        Lipid bilayers are fluid

                        Proteins may be designed to self-organize with lipid bilayers

            Molecular Recognition

                        Crane principles for molecular recognition

                        Atomicity limits the tolerance of combining sites


                        Biomolecules show flexibility at all levels

                        Flexibility poses great challenges for the design of bionanomachines


Chapter 5. Functional Principles of Bionanotechnology

            Information-Driven Nanoassembly

                        Nucleic acids carry genetic information

                        Ribosomes construct proteins

                        Information is stored in very compact form


                        Chemical energy is transferred by carrier molecules

                        Light is captured with specialized small molecules

                        Protein pathways transfer single electrons

                        Electrical conduction and charge transfer have been observed in DNA

                        Electrochemical gradients are created across membranes

            Chemical Transformation

                        Enzymes reduce the entropy of a chemical reaction

                        Enzymes create environments that stabilize transition states

                        Enzymes employ chemical tools to perform a reaction


                        Protein activity may be regulated through allosteric motions

                        Protein action may be regulated by covalent modification


                        Helical assembly of subunits forms filaments and fibrils

                        Microscale infrastructure is build from fibrous components

                        Minerals are combined with biomaterials for special applications

                        Elastic materials use disordered chains

                        Cells make specific and general adhesives

            Biomolecular Motors

                        ATP powers linear motors

                        ATP synthase and flagellar motors are rotary motors

                        Brownian ratchets rectify random thermal motions

            Traffic Across Membranes

                        Potassium channels use a selectivity filter

                        ABC transporters use a flip-flop mechanism

                        Bacteriorhodopsin uses light to pump protons

            Biomolecular Sensing

                        Smell and taste detect specific molecules

                        Light is sensed by monitoring light-sensitive motions in retinal

                        Mechanosensory receptors sense motion across a membrane

                        Bacteria sense chemical gradients by rectification of random motion


                        Cells are autonomous self-replicators

                        The basic design of cells is shaped by the processes of evolution

            Machine-Phase Bionanotechnology

                        Muscle sarcomeres



Chapter 6. Bionanotechnology Today

            Basic Capabilities

                        Natural proteins may be simplified

                        Proteins are being designed from scratch

                        Proteins may be constructed with non-natural amino acids

                        Peptide nucleic acids provide a stable alternative to DNA and RNA

            Nanomedicine Today

                        Computer-aided drug design has produced effective anti-AIDS drugs

                        Immunotoxins are targeted cell killers

                        Drugs may be delivered in liposomes

                        Artificial blood saves lives

                        Gene therapy will correct genetic defects

                        General medicine is changing into personalized medicine

            Self-Assembly at Many Scales

                        Self-assembled DNA scaffolds have been constructed

                        Cyclic peptides form nanotubes

                        Fusion proteins self-assemble into extended structures

                        Small organic molecules self-assemble into large structures

                        larger objects may be self-assembled

            Harnessing Molecular Motors

                        ATP synthase is used as a rotary motor

                        Molecular machines have been built of DNA

            DNA Computers

                        The first DNA computer solved a traveling salesman problem

                        Satisfiability problems are solved by DNA computing

                        A Turing machine has been built of DNA

            Molecular Design Using Biological Selection

                        Antibodies may be turned into enzymes

                        Peptides may be screened with bacteriophage display libraries

                        Nucleic acids with novel functions may be selected

                        Functional bionanomachines are surprisingly common

            Artificial Life

                        Artificial protocells reproduce by budding

                        Self-replicating molecules are an elusive goal

                        ATP is made with an artificial photosynthetic liposome

                        Poliovirus has been created using only a genetic blueprint

            Hybrid Materials

                        Nanoscale conductive metal wires may be constructed with DNA

                        Patterned aggregates of gold nanoparticles are formed with DNA

                        DNA flexes a sensitive mechanical lever

                        Researchers are harnessing biomineralization


                        Antibodies are widely used as biosensors

                        Biosensors detect glucose levels for management of diabetes

                        Engineered nanopores detect specific DNA sequences


Chapter 7. The Future of Bionanotechnology

                        A timetable for bionanotechnology

            Lessons for Molecular Nanotechnology

            Three Case Studies

                        Case study: Nanotube synthase

                        Case study: A general nanoscale assembler

                        Case study: Nanosurveillance

            Ethical Considerations

                        Respect for life

                        Potential dangers

                        Final thoughts