Physics of Bio-Molecules and Cells

Henrik Flyvbjerg, Frank Jülicher, Pal Ormos, Francois David3540441328, 9783540441328

Aimed at those working to enter this rapidly developing field, this volume on biological physics is written in a pedagogical style by leading scientists giving explanations that take their starting point where any physicist can follow and end at the frontier of research in biological physics. These lectures describe the state-of-the-art physics of biomolecules and cells. In biological systems ranging from single biomolecules to entire cells and larger biological systems, it focuses on aspects that require concepts and methods from physics for their analysis and understanding, such as the mechanics of motor proteins; how the genetic code is physically read and managed; the machinery of protein – DNA interactions; force spectroscopy of biomolecules’ velopes, cytoskeletons, and cytoplasms; polymerization forces; listeria propulsion; cell motility; lab-on-a-chip nanotechnology for single-molecule analysis of biomolecules; bioinformatics; and coding and computational strategies of the brain.

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Table of contents :
12.pdf……Page 0
Contents……Page 15
1.1.1 Two families……Page 16
1.1.2 Prokaryote gene expression……Page 18
1.2.1 Chemical structure of DNA……Page 21
1.2.2 Physical structure of DNA……Page 23
1.2.3 Chemical structure of proteins……Page 25
1.2.4 Physical structure of proteins……Page 27
2.1.1 The law of mass action……Page 29
2.1.2 Statistical mechanics and operator occupancy……Page 32
2.1.3 Entropy, enthalpy, and direct read-out……Page 33
2.1.4 The lac repressor complex: A molecular machine……Page 36
2.2.1 Reaction kinetics……Page 39
2.2.2 Debye–Smoluchowski theory……Page 41
2.2.3 BWH theory……Page 43
2.2.4 Indirect read-out and induced fit……Page 45
3.1.1 Eukaryotic gene expression and Chromatin condensation……Page 47
3.1.2 A mathematical experiment and White’s theorem……Page 50
3.2 The worm-like chain……Page 53
3.2.2 Nucleosomes and the Marky–Manning transition……Page 55
3.2.3 Protein-DNA interaction under tension……Page 58
3.2.4 Force-Extension Curves……Page 60
3.3.1 Structural sequence sensitivity……Page 63
3.3.2 Thermal fluctuations……Page 65
4 Electrostatics in water and protein-DNA interaction……Page 66
4.1 Macro-ions and aqueous electrostatics……Page 67
4.2 The primitive model……Page 69
4.2.2 The primitive model: DH regime……Page 70
4.3.1 Charge renormalization……Page 71
4.3.2 Primitive model: Oosawa theory……Page 72
4.3.3 Primitive model: Free energy……Page 74
4.4.1 Counter-ion release……Page 76
4.4.2 Nucleosome formation and the isoelectric instability……Page 77
References……Page 80
Contents……Page 83
1 Introduction……Page 84
2 Cell motility and motor proteins……Page 85
3 Motility assays……Page 86
4 Single-molecules assays……Page 88
5 Atomic structures……Page 90
6 Proteins as machines……Page 91
7 Chemical forces……Page 93
8 Effect of force on chemical equilibria……Page 94
9 Effect of force on the rates of chemical reactions……Page 95
10 Absolute rate theories……Page 98
11 Role of thermal fluctuations in motor reactions……Page 100
12 A mechanochemical model for kinesin……Page 102
13 Conclusions and outlook……Page 105
Contents……Page 109
1.1 Motor proteins and Carnot engines……Page 111
1.2 Simple Brownian ratchet……Page 112
1.3 Polymerization ratchet……Page 113
1.4 Isothermal ratchets……Page 116
1.5 Motor proteins as isothermal ratchets……Page 117
1.6 Design principles for e.ective motors……Page 118
2.1 Swinging lever-arm model……Page 121
2.2 Mechano-chemical coupling……Page 123
2.3 Equivalent isothermal ratchet……Page 124
2.4 Many motors working together……Page 125
2.5 Designed to work……Page 128
2.6 Force-velocity relation……Page 129
2.7 Dynamical instability and biochemical synchronization……Page 131
3.1 Dynamical instabilities……Page 132
3.2 Bidirectional movement……Page 133
3.3 Critical behaviour……Page 134
3.4 Oscillations……Page 137
3.5 Dynamic buckling instability……Page 138
3.6 Undulation of flagella……Page 140
4.1 System performance……Page 142
4.2 Mechano-sensors: Hair bundles……Page 143
4.3 Active amplification……Page 144
4.4 Self-tuned criticality……Page 146
4.5 Motor-driven oscillations……Page 147
4.6 Channel compliance and relaxation oscillations……Page 149
4.7 Channel-driven oscillations……Page 151
4.8 Hearing at the noise limit……Page 152
Contents……Page 158
1.1 Introduction……Page 159
1.1.2 Biomolecular complexity and role for dynamic force spectroscopy……Page 160
1.1.3 Biochemical and mechanical perspectives of bond strength……Page 162
1.1.4 Relevant scales for length, force, energy, and time……Page 165
1.2 Brownian kinetics in condensed liquids: Old-time physics……Page 166
1.2.1 Two-state transitions in a liquid……Page 167
1.2.2 Kinetics of first-order reactions in solution……Page 168
1.3.1 Dissociation of a simple bond under force……Page 170
1.3.2 Dissociation of a complex bond under force: Stationary rate approximation……Page 171
1.3.3 Evolution of states in complex bonds……Page 175
1.4 Testing bond strength and the method of dynamic force spectroscopy……Page 176
1.4.1 Probe mechanics and bond loading dynamics……Page 177
1.4.2 Stochastic process of bond failure under rising force……Page 180
1.4.3 Distributions of bond lifetime and rupture force……Page 181
1.4.4 Crossover from near equilibrium to far from equilibrium unbonding……Page 184
1.4.5 Effect of soft-polymer linkages on dynamic strengths of bonds……Page 187
1.4.6 Failure of a complex bond and unexpected transitions in strength……Page 189
1.5 Summary……Page 197
References……Page 198
2.1 Hidden mechanics in detachment of multiple bonds……Page 199
2.2 Impact of cooperativity……Page 200
2.3.1 Markov sequence of random failures……Page 203
2.3.2 Multiple-complex bonds……Page 205
2.3.3 Multiple-ideal bonds……Page 206
2.3.4 Equivalent single-bond approximation……Page 207
2.4.2 Equivalent single-bond approximation……Page 210
2.5 Poisson statistics and bond formation……Page 211
2.6 Summary……Page 215
References……Page 216
Contents……Page 227
1 Introduction……Page 228
2.1 A little chemistry……Page 229
3.1 Motion in the laboratory frame……Page 231
3.2 Propulsion and steady velocity regimes……Page 232
3.3 Gel/bacterium friction and saltatory behaviour……Page 234
4.1 A spherical Listeria……Page 236
4.2 Spherical symmetry……Page 237
4.3 Steady state……Page 238
4.5 Symmetry breaking……Page 240
4.6 Limitations of the approach and possible improvements……Page 242
5 Conclusion……Page 245
References……Page 246
Contents……Page 249
1.1 The lipid/protein bilayer is a multicomponent smectic phase with mosaic like architecture……Page 250
1.2 The spectrin/actin cytoskeleton as hyperelastic cell stabilizer……Page 253
1.3 The actin cortex: Architecture and function……Page 256
2.1 Actin is a living semiflexible polymer……Page 260
2.2 Actin network as viscoelastic body……Page 264
2.3 Correlation between macroscopic viscoelasticity and molecular motional processes……Page 269
3.1 Manipulation of actin gels……Page 271
3.2 Control of organization and function of actin cortex by cell signalling……Page 276
4 Micromechanics and microrheometry of cells……Page 278
5 Activation of endothelial cells: On the possibility of formation of stress fibers as phase transition of actin-network triggered by cell signalling pathways……Page 282
6 On cells as adaptive viscoplastic bodies……Page 285
7 Controll of cellular protrusions controlled by actin/myosin cortex……Page 289
References……Page 293
Contents……Page 297
1 Introduction……Page 298
2 Mimicking cell adhesion……Page 303
4 Soft shell adhesion is controlled by a double well interfacial potential……Page 305
5 How is adhesion controlled by membrane elasticity?……Page 308
6 Measurement of adhesion strength by interferometric contour analysis……Page 310
8 Measurement of unbinding forces, receptor-ligand leverage and a new role for stress fibers……Page 311
10 Conclusions……Page 314
A Appendix: Generic interfacial forces……Page 315
References……Page 319
Contents……Page 322
1 Why micro/nanofabrication?……Page 324
1 Introduction: The need to control flows in 2 1/2 D……Page 328
2 Somewhat simple hydrodynamics in 2 1/2 D……Page 330
3 The N-port injector idea……Page 337
References……Page 342
1 Introduction……Page 344
2.1 Fabrication……Page 346
2.4 DNA samples……Page 347
3.1 Basic results and dielectrophoretic force extraction……Page 348
4 Data and analysis……Page 352
5 Origin of the low frequency dielectrophoretic force in DNA……Page 356
6 Conclusion……Page 362
References……Page 363
1 Introduction……Page 365
2 Experimental approach……Page 369
3 Conclusions……Page 373
References……Page 374
2 Design……Page 375
3 Results……Page 376
4 Conclusions……Page 381
References……Page 382
1 The problems with insulators in rachets……Page 383
2 An experimental test……Page 384
References……Page 390
1 Introduction……Page 391
2 The nearfield scanner……Page 392
3 The chip……Page 393
4 Experiments with molecules……Page 396
References……Page 400
2 Blood specifics……Page 401
3 Magnetic separation……Page 406
4 Microfabrication……Page 407
5 Magnetic field gradients……Page 408
6 Device interface……Page 410
7 A preliminary blood cell run……Page 415
8 Conclusions……Page 418
References……Page 419
1 Introduction……Page 420
2 Technology……Page 421
3 Experiments……Page 424
References……Page 427
Contents……Page 430
1 Introduction……Page 431
2 New technologies……Page 433
3 Sequence comparison……Page 435
4 Clustering……Page 438
5 Gene regulation……Page 440
References……Page 441
Contents……Page 444
1 Enzymatic networks. Proofreading knots: How DNA topoisomerases disentangle DNA……Page 446
1.1 Length scales and energy scales……Page 447
1.2 DNA topology……Page 448
1.3 Topoisomerases……Page 449
1.4 Knots and supercoils……Page 452
1.5 Topological equilibrium……Page 454
1.6 Can topoisomerases recognize topology?……Page 455
1.7 Proposal: Kinetic proofreading……Page 456
1.8 How to do it twice……Page 457
1.9 The care and proofreading of knots……Page 459
1.10 Suppression of supercoils……Page 461
1.11 Problems and outlook……Page 463
2.1 The regulation of gene expression……Page 465
2.2 Gene expression arrays……Page 468
2.3 Analysis of array data……Page 471
2.4 Some simplifying assumptions……Page 472
2.5 Probeset analysis……Page 474
2.6 Discussion……Page 478
3 Neural and gene expression networks: Song-induced gene expression in the canary brain……Page 479
3.1 The study of songbirds……Page 480
3.2 Canary song……Page 481
3.3 ZENK……Page 482
3.5 Histological analysis……Page 484
3.6 Natural vs. artificial……Page 487
3.7 The Blush II: gAP……Page 488
3.8 Meditation……Page 489
References……Page 490
Contents……Page 493
1 Introduction……Page 494
2 Photon counting……Page 498
3 Optimal performance at more complex tasks……Page 508
4 Toward a general principle?……Page 525
5 Learning and complexity……Page 545
6 A little bit about molecules……Page 559
7 Speculative thoughts about the hard problems……Page 571
References……Page 580