Inhaltsverzeichnis

Vorwort

Preface

The concept of force spectroscopy is deceptively simple: if we could attach a pair of handles to two interacting molecules and use those handles to pull the molecules apart, then we could not only obtain a clear and unambiguous value of the bond strength, but also obtain this value with a very direct and straightforward measurement. People have used the "tug test" to measure and compare strength in many forms throughout history and ooccasionally this strength testing could take the entertaining form of a "tug-of-war" contest, such as the Japanese tsunahiki. Tug-of-war even used to be an Olympic sport in the beginning of the twentieth century. We all have certainly played with the force-measuring springs in a science class at school. So what could be simpler than pulling two species apart?

At least that was my impression when I first got exposed to the concept of using tiny springs to probe molecular-scale interactions. At the time, I was a very green and moderately scared first year graduate student at Harvard who, along with the rest of my classmates, was looking for a research project and for a research group to call home for the next several years. The choice process consisted mostly of listening to gossip, going to each group's open house, and then gossiping more. Although the conversations mostly revolved around the free pizza typically served at those functions, a good deal of the professors' research presentations was also discussed. I still remember being very impressed by two events at the open house of Charles Lieber' s group. First, instead of the perfectly respectable but boring pizza, the Lieber group served a lavish Chinese takeout buffet, which was met with considerable delight by everyone in attendance. Second, the research presentation mentioned a project where someone would try to attach specific molecules to the needle of an AFM probe and then use specific interactions of those molecules to perform chemically specific imaging at that unprecedentedly small scale. The concept, which later would become known as chemical force microscopy, had a strange appeal to me, which I immediately shared with my classmate sitting on the conference room floor next to me. His response had a noticeable sarcastic overtone: "Good luck doing it, it sounds complicated...." Like any good advice, it went unheeded, and after a few days of deliberations I signed on. Thus my decade-long fascination with force spectroscopy and its applications to the study of chemical and biological interactions started. Today I would freely admit that the advice I received from my classmate was quite sound. Over the past decade, it has been indeed fascinating to watch researchers uncover an incredibly rich universe of different physical behaviors that originate from such a conceptually simple setup.

Why do researchers continue to be interested in interaction forces when everything we study in the physics, chemistry, and biophysics courses almost always revolves around interaction energies and interaction potentials? Part of the answer lies in the ubiquitous role the interaction forces play in the majority of condensed phase phenomena. These interactions ultimately shape the dynamics of the molecular behavior on the microscopic scale, and direct probing of interaction forces is important for compiling the full picture of these phenomena. Often these processes, most notably in biological systems, involve spectacular rearrangements and movements of ions, molecules, or whole molecular assemblies driven by mechanical stresses generated by molecular-scale motors. Direct probing of the forces generated by these sophisticated biological machines provides invaluable information about the nature of these processes, and force spectroscopy techniques have been at the forefront of molecular motor studies. Perhaps the most powerful argument for the utility of force spectroscopy techniques is that they provide researchers with a "handle" that they can use to deform the potential energy landscape in the direction of the applied force. Such deformation invariably modifies the kinetics of the molecular bond rupture, and monitoring of the rupture kinetics as a function of the applied force (and force direction) gives us a unique opportunity to study the potential energy landscape of the interactions, often in one direction at a time.

A force spectroscopy measurement almost always involves attaching interacting molecules to a force transducer and then using a mechanical translation device, such as a piezoelectric scanner, to move one of the interacting molecules. In practice, this scheme can be implemented using a large number of very distinct technical approaches. Three of them tend to dominate the force spectroscopy field nowadays. The surface forces apparatus uses ultrasmooth crossing cylinder sheets to probe the interactions between monolayers of interacting species attached to the surfaces of the interacting sheets. Optical and magnetic trapping techniques, which are widely known as "molecular tweezers" techniques, use optical gradients of magnetic fields to trap and move tiny particles or beads. Researchers can use a well-developed arsenal of chemical and biochemical methods to tether different configurations of molecules to the bead surfaces, use the trap to manipulate the beads, and then use highly controlled small forces to study the interaction dynamics. Finally, perhaps the most widespread technique involves using tiny atomic force microscope probes to measure interaction forces between molecules attached to the surfaces of the cantilever tip and the sample.

Each of these measurements addresses several common questions and challenges. First, researchers need to design the experiment to enable probing of a certain specific interactions while discriminating against the non-specific interactions that are always present in real measurements. Second, more often than not, force spectroscopy measurements happen away from equilibrium; therefore researchers need to pay attention to the kinetics of the loading and rupture process and use this information to reconstruct the underlying potential energy landscape of the intermolecular bond. Third, manipulating single molecules on the nanometer scale is rarely precise and researchers are always facing the challenge of estimating properly the number of interacting molecules and relating that to the measured forces.

This book is not intended as a mere survey of the force spectroscopy achievements over nearly two decades of the field's existence, as such surveys are almost always incomplete in an actively developing field. Instead, the intent is to present a series of topics that discuss fundamental concepts and basic methodology used to perform and understand force spectroscopy experiments and illustrate them using examples from current and past research. Thus the ideal audience that we have imagined for this book is a graduate student who is just starting in the force spectroscopy field and is looking to learn the ropes, or a researcher from an adjacent field who wants to get up to speed with force spectroscopy measurements, or simply wants to evaluate the potential benefit of the technique for her research. Our hope is that this audience will be served well by the material presented in this handbook.

D. Leckband starts the volume by describing the basic principles of the surface forces apparatus measurements and their applications for studies of the protein-protein interactions. C. Lieber, A. Noy, and D. Vezenov give a detailed description of chemical force microscopy-the technique for probing intermolecular interactions using AFM tips functionalized with specific chemical functional groups. R. Conroy presents an extensive survey of the force measurements using magnetic and optical tweezers-the technique that in many aspects is complementary to the AFM and SFA-based measurements.

One of the major advancements in force spectroscopy in the last decade has been the emergence of the kinetic model of the bond strength, which caused a paradigm shift in the interpretation of force spectroscopy experiments and spawned the development of dynamic force spectroscopy. A chapter by P. Williams discusses dynamic force spectroscopy and its applications to the AFM experiments. A contribution by K. Anderson, D. Brockwell, S. Radford, and D. A. Smith describes elegant experiments that use dynamic force spectroscopy to probe protein structure.

Functionalization of the force probes with biological molecules is an extremely important part of any force spectroscopy measurement, and the chapter by C. Blancette, A. Loui, and T. Ratto surveys different approaches to functionalization of the force probes. Attaching biomolecules to the force probes via long flexible polymeric tethers has proven to be an extremely versatile, important, and fruitful approach to such functionalization. The chapter by T. Sulchek, R. Friddle, and A. Noy discusses the implementation of this approach, the models used to interpret the results of these measurements, and their application to studies of the strength of multiple bonds. Development of the approaches to probe equilibrium potential energy landscapes of the interactions remains an important goal of the field, and a chapter by P. Ashby describes the design principles and the setup of the AFM measurements that could allow direct reconstruction of this energy landscape. Finally, the continuing explosive growth of the computing power available to researchers brings molecular modeling to the forefront of force spectroscopy research. D. Patrick presents an overview of the modeling of force spectroscopy experiments, with an emphasis on analyzing chemical force microscopy measurements.

I hope that this book will convey a sense that as a result of the last decade of force spectroscopy development our knowledge of the behavior of a non-covalent chemical bond under an external load is immeasurably richer; yet, at the same time, that we now understand the limitations and the complications of the technique with more clarity. The naïve optimism of the first years of force spectroscopy has been replaced with more realistic expectations rooted in the deep understanding of the physical processes underlying the measurements.

I would like to thank numerous individuals who helped with various stages of this project. First and foremost, I am indebted to the book's contributors for taking the time to summarize their respective areas of research. This book has been partly inspired by the works presented at the symposium on "Nanoscale Probing of Intermolecular Interactions" at the 2005 ACS National Meeting. V.V. Tsukruk has been an early supporter of the idea of this symposium and I thank him for his help and encouragement. David Packer at Springer has been a great editor and I thank him for his patience and for his helping hand. Finally, I thank my wife and my two daughters for their support and patience.

Aleksandr Noy

Lawrence Livermore National Laboratory

Livermore, CA

June 28, 2007

Klappentext

Handbook of Molecular Force Spectroscopy

Aleksandr Noy

Editor

Modern materials science and biophysics are increasingly focused on studying and controlling intermolecular interactions on the single-molecule level. Molecular force spectroscopy was developed in the past decade as the result of several unprecedented advances in the capabilities of modern scientific instrumentation, and defines a number of techniques that use mechanical force measurements to study interactions between single molecules and molecular assemblies in chemical and biological systems. Examples of these techniques, which typically target a specific range of experimental systems and geometries, include atomic force microscopy, optical tweezers, surface forces apparatus, and magnetic tweezers.

With contributions by internationally renowned scientists, Handbook of Molecular Force Spectroscopy is a comprehensive, state-of-the-art review of modern force spectroscopy, including fundamentals of intermolecular forces, technical aspects of the force measurements, and practical applications. The Handbook reviews the fundamental physical concepts of loading single and multiple chemical bonds on the nanometer scale, covers practical aspects of modern single-molecule level techniques, and describes a number of representative applications of force spectroscopy to the study of chemical and biological processes. Computer modeling of force spectroscopy experiments is addressed as well. In sum, this volume is an authoritative guide to planning, understanding, and analyzing modern molecular force spectroscopy experiments with an emphasis on biophysical research.

ISBN 978-0-387-49987-1

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Index

A

Ab initio calculations, 126, 167
Acid-base interactions, 109, 110
Actin, 67-68, 70, 74-76, 83, 205, 240
Adhesion
- energy, 6-7, 9-12, 177, 178
- force, 99, 101-105, 108-111, 113-115, 124-132, 137, 138, 185, 261
- force distribution, 108, 110
- width, 110
- protein-protein, 10
- map, 108, 138
- measurement, 1, 17, 110, 112, 128, 130, 133, 139
Adhesion mapping, 261
Affinity, 59-61, 143, 193, 207, 211, 213, 225, 251
AFM. See Atomic Force Microscopy AFM cantilever, 98, 102, 144, 148, 153, 154, 157, 158, 172, 186, 187, 189-192, 268, 279
AFM tip cleaning, 186-187
AFM tip functionalization
- by esterification, 185, 186, 188-190, 193, 196, 199
- with SAMs, 193
- by silanization, 185, 186, 188-190, 193, 196, 199

- 3-aminopropyl triethoxysilane (APTES), 124-126, 188, 196, 199, 200
- silanization with, 125, 188, 196, 199, 200
Applied load force, 112, 113, 131, 132
Atomic Force Microscopy, 6, 8, 9, 15, 19, 24, 29, 55, 61, 66, 68, 69, 71, 97, 168, 185, 252, 261
ATPase, 74-76

B

Beam
Bessel, 38-39
- Hermite Gaussian, 36-37
- Laguerre-Gaussian, 37-38
Bell model, 60, 257
Bending modulus
- of polymer chain, 254, 255
BFPR. See Brownian Force Profile Reconstruction Biological adhesion
- cell adhesion, 1, 9, 13, 14, 17, 18, 198, 199, 234
Biomembrane Force Probe, 148, 155, 167, 168, 207, 208, 232, 261
Biopolymers, 40, 44, 60, 63-72, 83, 173
Bond
- lifetime, 168, 269
- multiple, 6, 17, 147, 258, 263, 264, 267, 268
single, 6, 7, 15, 116, 117, 150, 251-270
strength, 2, 103, 117-119, 128, 150, 252, 263, 265, 268, 270
Brownian Force Profile Reconstruction (BFPR), 282-285
Brownian motion, 31, 46, 54-57, 275, 284
Bungee cords
- isolation with, 279

C

Cadherin, 9, 17, 80, 234, 236
Calibration
- using equipartition theorem. See Using power spectrum analysis
- lateral spring constant of AFM cantilever, 102
- normal spring constant of AFM cantilever, 102
- of optical trap force, 32, 46, 50, 53
- using power spectrum analysis, 57-59
- using viscosity, 56-57, 59
Cantilever
- damping, 138, 279
- feedback techniques, 280
- optimization, 278-282
Cantilever spring constant
- lateral, 102
- normal, 98, 102
Capillary adhesion. See Capillary forces Capillary forces, 101, 102, 136
Carbon nanotube CFM, 111
Cell manipulation, 80
CFM. See Chemical Force Microscopy CFT. See Chemical Force Titration Chemical Force Microscopy, 97, 99, 101-105, 108, 110-112, 114-117, 119, 120, 123-140, 172, 176, 186, 192, 198, 200, 201
Chemical Force Spectroscopy. See Chemical Force Microscopy
Chemical Force Titration, 124-127, 129, 140
Chiral isomer discrimination
- in CFM experiment, 114
Coarse grained model, 229
Communication bottleneck, 173
Conformation transitions, 255, 256, 258
Constant charge conditions, 130
Constant potential conditions, 130
Contact angle, 113-115, 124-126
Contact area
- tip-sample, 111
Contact mechanics models
- DMT model, 107, 177
- JKR model, 107, 113, 177, 178
Contact mode imaging, 136
Contour length, 44, 63, 68-70, 149, 156, 214-217, 227, 233, 241, 253-259, 261, 265
Counting individual bonds, 263-265

D

Damping, 49, 98, 137, 138, 210, 257, 274-276, 279, 280, 282, 284
Debye screening length, 130
DEP traps. See Dielectrophoretic traps Derjaguin approximation, 5, 6
Derjaguin-Miiller-Toporov theory. See Contact
- mechanics models: DMT model DFS. See Dynamic force spectroscopy Dielectric trapping force, 26
Dielectrophoretic traps (DEP), 26
Diffraction
- effect on optical lever detection, 98
Dispersion force, 108, 109
Dissociation kinetics, 143, 147, 158, 199
Dissociation rate, 55, 60-62, 143, 144, 147, 257, 263
DNA, 35, 38, 43, 44, 55, 63-67, 71-74, 117, 185, 192, 193, 195, 207, 211, 212, 235
Double layer, 123, 126, 129-131, 133, 273
Dugdale approximation, 107
Dynamic Force Spectroscopy (DFS), 143-159, 253, 257, 268-270
phenomenological model, 146-148, 158
Dynamic force spectrum, 145-151, 155, 229, 232, 268
Dynamic recognition force mapping, 261, 262
Dynein, 78

E

ED-CFM.
See Energy Dissipation Chemical Force
- Microscopy Effective probe radius, 111
eFJC.
See Extensible freely-joined chain model Electrostatic field, 26
Empirical force field, 166, 167
Enclosures
- acoustic, 279
- vibration, 279
Energy
- Gibbs free, 7
- interfacial free, 106, 113, 119, 126, 137
Energy dissipation, 24, 123, 124, 136, 137, 139, 140
Energy Dissipation Chemical Force Microscopy
- (ED-CFM), 137
Energy dissipation imaging, 136
Energy minimization, 165
Entropie barriers, 117-119
Entropie spring, 149, 173, 214, 242, 253
Esterification, 185, 186, 188-190, 193, 196, 199
Evaporation, 50, 191, 192, 213
eWLC.
See Extensible worm-like chain model Exonuclease, 71-72
Extensible freely-jointed chain model, 255, 256, 258, 259
Extensible worm-like chain model, 255
Extension
- of multiple identical tethers, 265-266

F

F-D curve, 98, 104, 130
Feedback loop
- gain, 280, 281
- stabilizing, 281
Ferrofluids, 48, 49, 179
FJC.
See Freely-jointed chain Fluorescence markers
- tagging with, 52
Force curve, 6, 10, 66, 98, 99, 102, 104, 170-173, 176-178, 189, 260, 264, 274, 275, 282, 283
Force-distance profile, 5, 9, 10, 12, 15
Force, inter-membrane, 60
Force profile, 6, 11, 15, 98, 130, 131, 169, 274, 275, 279-285
Force spectroscopy
- on cellular and system-level, 79-82
- of enzymes with optical tweezers, 71-74
- inter-and intra-molecular using optical tweezers, 60-79
- membrane and cytoplasm, 79-80
Force titration curve, 126
Freely jointed chain (FJC), 63, 64, 254-256, 258, 259
Friction contrast, 134-136
Friction force, 108, 112, 113, 119, 123, 131-136, 138, 139, 287
Friction loop, 102, 131
Functionalization
- of AFM probes, 137
- of surfaces, 123, 273

G

Gaussian chain, 255
Giant magnetore si stive sensors, 43
Glue model, 166
Gradient force, 28-29, 32, 40, 42
Gyrase, 73

H

Hall sensors, 43
Harmonic oscillator, simple, 274, 275, 284
Helicase, 72-73,
Hierarchical modeling schemes, 167
Histogram
- of rupture forces, 152, 153, 253
Hydrodynamics
- effect on AFM cantilevers, 156
Hydrogen bond strength, 128
Hydrophilic group, 101, 126, 127, 133
Hydrophobic group, 126

I

Ig domains
- unfolding of, 255
Imaging, 4, 8, 9, 23-25, 32-34, 40, 41, 48-53, 57, 63
Interaction potential(s), 98, 99, 117, 164, 273-275, 279, 280, 282, 284, 285
- direct mapping of, 273-285
- empirical, 164
Interactions
- hydrogen bonding, 104, 109, 114, 115
- protein, 1, 15, 19, 221, 225
- van der Waals, 60, 98, 104, 105, 108-110, 175, 179, 193, 196, 273
Interfacial force microscope, 99, 177
Interferometer
Fabry-Perot, 2, 3
- Intermediate filaments, 68, 83
Intermolecular force components theory, 108-110
Intermolecular interactions, 98, 104, 105, 109, 119, 123, 124, 140, 166, 185, 273-275, 285
Intermolecular potential, 100, 164, 273, 275
InvOLS.
See Sensitivity, of optical lever Ionization
- of surface groups, 124, 133
Isolation
- acoustic, 54, 278, 279
- active vibration, 279
- vibration, 54, 278, 279
Isotropic fluid, 179

J

Johnson-Kendall-Roberts theory.
See Contact mechanics
- model: JKR model Jump to contact, 281

K

Kinesin, 60, 74, 76-78, 205, 207
Kinetic model, 117-119
Kinetic regime
- in CFM experiments, 116, 117
Kuhn statistical segment length, 254

L

Langmuir-Blodgett film, 8, 133
Lateral force imaging, 134-136
Lévitation, 23, 25
Ligand-receptor interactions, 60-62, 174, 175, 252
Linkers
- flexible polymer, 251
- PEG, 266
Linking
- molecules to surfaces with tethers, 252
Loading
- activated regime, 168-169
- friction regime, 168-170
Loading rate, 7, 34, 55, 60, 61, 66, 111, 116, 117, 136, 145
Lubrication, 97, 176

M

Macromolecules, 1, 2, 117, 124, 257
Magnetic field, 23, 24, 26, 27, 40-44, 46-50, 57, 75, 81, 84, 179, 205, 210
Magnetic force
- theory of, 41-44
Magnetic force feedback, 130, 131
Magnetic particles
- superparamagnetic, 40, 43, 44, 48, 49
Magnetic trap
- construction and characterization, 50-59
Magnetic tweezers
- electromagnet, 45, 47-48
- permanent, 46
Markovian model of bond dissociation, 251
MC.
See Monte Carlo simulation MD simulations.
See Molecular dynamics
- simulations Metal deposition
- on AFM tips, 185, 186, 190-192
Micromanipulation, 23
Microtubules, 63, 68, 70, 77, 78, 80, 83, 205
MM.
See Molecular mechanics Molecular dynamics simulation, 12, 164, 168, 170-177, 180, 221-225, 227, 228, 238, 239
Molecular mechanics (MM), 76, 165-167
Molecular modeling, 173
Molecular motors, 44, 60, 74-79
Monte Carlo simulation, 150, 153, 164, 165, 182, 217, 218, 230, 231
Multiple bonds
- correlated bonds, 116
- strength of, 267
- uncorrected bonds, 116, 268-270
Multivalent binding, See Multivalent
- interactions Multivalent interactions, 251, 262, 265, 269, 270
Myosin, 68, 74, 76-78, 205, 207, 233, 234

N

Neural Cell Adhesion Molecule (NCAM), 9, 13-19
N-hydroxysuccinimide, 188, 196, 198, 199
Noise
- flicker, 275-277, 279
- power spectrum of, 275, 278
- shot, 54, 277
- thermal, 25, 98, 150, 158, 210, 211, 235, 238, 275-277, 279, 280, 282-284
- white, 58, 275, 277, 284
Non-contact micromanipulator, 33, 50
Non-equilibrium unbinding, 116
Numerical aperture, 32, 48, 50, 51, 278, 279, 282, 285

O

Optical beam, 33, 35, 36, 38
Optical lever
- inverse sensitivity (INVOLS), 277
- sensitivity errors, 148-149
Optical trap
- construction and characterization, 50-59
- holographic, 35-37
- light source for, 34, 50, 51
- multiple beam, 34-35
- near-field, 36
objective for, 32-36, 50-51
- piezoelectric stage for, 50, 51, 53
- single beam, 32-34
- three dimensional, 25
Optical tweezers, 24-44, 46, 48-51, 54-56, 61

P

Parallel bond configuration, 263
Parallel loading, 117
Particle tracking, 52-55
Particles
- suitable for trapping, 26, 39
PEG extension, 258-259
Persistence length, 44, 63, 64, 66-71, 83, 149, 214, 252, 254, 255
Poisson statistics model, 267
Polarizability, 26, 28, 84, 109
Polyethyleneglycol (PEG), 188, 192, 193, 195, 196, 198-200, 255, 257-259, 261, 265-268
Polyethyleneoxide (PEO), 256, 259
Polymer chain, 71, 252, 253, 255, 256, 258
Polysaccharides, 69-71, 80, 83, 233, 259
Polyubiquitin, 169
Potential
- Gay-Berne, 180, 181
- Lennard-Jones, 107, 108, 180
Potential energy barrier, 119, 147, 268
Potential energy landscape, 282
- tilting with applied force (Not found) Power spectral density, 58, 59, 244, 275
Probe size effects, 1 10

Q

Q-control, 138, 280, 281, 284
Quality factor
- of AFM cantilever, 98, 136
Quantum mechanical calculations, 165, 167, 259
Quasi-equilibrium unbinding, 113

R

Radiation pressure
- theory of, 26-32
Rayleigh regime, 31
Ray optics regime, 31-32
Reflective coating, 277
Resonant frequency
- of AFM cantilever, 136
RMS noise, 275, 280
RNA, 63, 66, 67, 71, 72, 81, 146, 155, 207
RNA polymerase, 72
Rupture force
- mean, 157
- mode, 151
- most probable, 146, 147, 151, 152, 269

S

Salt-bridges
contribution to adhesion, 9
- SAMs.
See Self-assembled monolayers
- pattened, 134, 139
Scaling relationships
- in CFM experiments, 110-116
Scanning Probe Microscopy, 97-98
Scattering force, 26, 28-31, 34, 35
Self-assembled monolayers
- mechanical properties, 114, 133
silanes, 101, 133
- thiols, 100, 101, 103, 125, 131, 134, 193-195, 199
Sensitivity
- distance sensitivity, 2
- force sensitivity, 6, 61, 97, 98, 155, 210, 279
- of optical lever, 148, 277
Separation distance
absolute, 2-4
- Serial loading
- of identical bonds, 116
Shear stress, 112, 113, 131, 198, 199
SFA.
See Surface Forces Apparatus Silanization
- vapor phase, 125, 189, 200
Simulation timescale, 167-173, 182
Single-asperity contact, 112
Single molecule measurements, 1, 6, 24, 60, 76, 265
Snap to contact.
See Jump to contact Solvation forces, 175, 273
Solvent polarity
- role in CFM experiments, 114
Spatial coherence, 36
Spring
- non-Hookean, 253
Spring constant
- calibration, 102, 148, 149, 284
sensitivity errors, 148-149
Sputtering, 191, 192
Steered MD.
See Steered Molecular Dynamics
Simulations Steered Molecular Dynamics (SMD) Simulations, 11, 12, 221, 224, 227, 234, 238
Stiffness
- of AFM cantilevers.
See AFM cantilever, normal spring constant of
- of polymer chain, 253
Streptavidin, 8, 9, 61, 62, 75, 147, 148, 158, 173-175, 208
Stretching modulus, 64, 67, 254, 255
Supported lipid bilayers, 8
Surface charge, 124, 126, 129, 130
Surface Forces Apparatus, 99, 167, 168, 175, 273
Surface free energy, 113-116, 124, 130
Surface roughness, 110, 111, 277
Surface tension, 105, 110, 115-117, 130
Surface tension component model, 105, 117

T

Tapping mode imaging, 136, 138
Temporally hybrid method, 172
Tether.
See Linker Tethered ligand systems, 270
Thermal fluctuations
- of AFM cantilever, 153
- role of, 42
Thermal noise, 25, 98, 150, 158, 210, 211, 235, 238, 275-277, 279, 280, 282-284
Tip radius, 102, 103, 111, 112, 114, 130, 177
Tip shape reconstruction, 102
Topoisomerase, 73, 74
Torque, 36, 38, 44, 46, 47, 64, 65, 74, 75, 78, 79
Tracking resolution
- limitations to, 54
Trajectory of states, 164
Transition state
- distance to, 252, 269
Transition state theory, 169

U

Ubiquitin, 169, 218, 220, 221, 232, 238-240, 242
Unfolding
- of protein molecules, 242

V

Vapor deposition
- chemical (CVD), 191
- physical (PVD), 191
Video tracking systems, 53

W

WLC.
See Worm-like chain
Work of adhesion, 6, 102, 106, 109, 111, 114-116, 137, 138, 178
Worm-like chain, 63, 67, 69, 149-151, 214-217, 227, 228, 254, 255, 260, 261

Autor

Contributors

Kirstine L. Anderson, Astbury Centre for Structural Molecular Biology, University of Leeds, Garstang Building, University of Leeds, Leeds, LS2 9JT, United Kingdom, bmbkla@ leeds.ac.uk

Paul D. Ashby, Molecular Foundry, Materials Sciences Division, Lawrence Berkeley National Laboratory, Mail Stop 67R2206, 1 Cyclotron Road, Berkeley, California 94720, USA, PDAshby@lbl.gov

Craig D. Blanchette, Chemistry, Materials and Life Sciences Directorate, Lawrence Livermore National Laboratory, L-454, 7000 East Ave, Livermore, CA 94550, USA, blanchette2@llnl.gov

David J. Brockwell, Astbury Centre for Structural Molecular Biology, University of Leeds, Garstang Building, University of Leeds, Leeds, LS2 9JT, United Kingdom, d.j .brockwell @ leeds.ac.uk

Richard Conroy, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health LFMI-10 Center Drive Bldg. 10, Rm. 3D17, MSC 1065, Bethesda, MD 20892, USA, conroyri@mail.nih.gov

Raymond W. Friddle, Chemistry, Materials and Life Sciences Directorate, Lawrence Livermore National Laboratory, L-234, 7000 East Ave, Livermore, CA 94550, USA, friddlel@llnl.gov

Deborah E. Leckband, Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, 127 Roger Adams Lab MC-712, Box C-3 600 S. Mathews Ave. Urbana, IL 61801, USA, leckband@uiuc.edu

Charles M. Lieber, Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA, cml@cmliris.harvard.edu

Albert Loui, Chemistry, Materials and Life Sciences Directorate, Lawrence Livermore National Laboratory, L-231, 7000 East Ave, Livermore, CA 94550, USA, loui2@llnl.gov

Aleksandr Noy, Chemistry, Materials and Life Sciences Directorate, Lawrence Livermore National Laboratory, L-234, 7000 East Ave, Livermore, CA 94550, USA, noyl@llnl.gov

David L. Patrick, Advanced Materials Science & Engineering. Center, Department of Chemistry, Western Washington University, 516 High St., Bellingham, WA 98225, USA, patrick@chem.wwu.edu

Sheena E. Radford, Astbury Centre for Structural Molecular Biology, University of Leeds, Garstang Building, University of Leeds, Leeds, LS2 9JT, United Kingdom, s.e.radford@leeds.ac.uk

Timothy V. Ratto, Chemistry, Materials and Life Sciences Directorate, Lawrence Livermore National Laboratory, L-231, 7000 East Ave, Livermore, CA 94550, USA, ratto7@llnl.gov

D. Alastair Smith, Chief Executive, Avacta Group plc, York Biocentre, Innovation Way, York Science Park, Heslington, York YO10 5NY, United Kingdom, phydams@ds.leeds.ac.uk

Todd A. Sulchek, Chemistry, Materials and Life Sciences Directorate, Lawrence Livermore National Laboratory, L-231, 7000 East Ave, Livermore, CA 94550, USA, todds@llnl.gov

Dmitry V. Vezenov, Department of Chemistry, Lehigh University, 6 E. Packer Ave., Bethlehem, PA 18015, USA, dvezenov@lehigh.edu

Phil M. Williams, Laboratory of Biophysics and Surface Analysis, School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom, phil.williams@nottingham.ac.uk

Reviews

From the reviews: "A series of ten chapters on various aspects of force spectroscopy, each written by an expert in the field. This book ... aims 'to present a series of topics that discuss fundamental concepts and basic methodology used to perform and understand force spectroscopy experiments and illustrate them using examples from current and past research.' This work would represent a good introduction to the area for anyone wishing to know more about this increasingly important subject. Summing Up: Highly recommended. Upper-division undergraduate through professional collections." (A. Fry, CHOICE, Vol. 45 (10), June, 2008) "A broad overview of core principles of force spectroscopy is of considerable utility and timeliness. Aleksandr Noy ... has done an admirable job of assembling such an overview as well as providing insight into likely new directions of research. ... a timely and useful summary of fundamental aspects of molecular force spectroscopy, and I believe it would make a worthwhile addition to any good scientific library. New research groups that are entering this field would be well advised to study this handbook ... ." (Matthew F. Paige, Journal of the American Chemical Society, Vol. 130 (26), 2008) "In this nicely produced volume, one of the subject's key architects and proponents presents an extremely timely and effective summary of the field. The content is well judged ... . Overall, this book represents a very worthwhile and up-to-date introduction to an exciting new field of optics." (Optics and Photonics News, July/August, 2008)