Physics of biomolecules and cells

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Contents......Page 16
1.1.1 Two families......Page 17
1.1.2 Prokaryote gene expression......Page 19
1.2.1 Chemical structure of DNA......Page 22
1.2.2 Physical structure of DNA......Page 24
1.2.3 Chemical structure of proteins......Page 26
1.2.4 Physical structure of proteins......Page 28
2.1.1 The law of mass action......Page 30
2.1.2 Statistical mechanics and operator occupancy......Page 33
2.1.3 Entropy, enthalpy, and direct read-out......Page 34
2.1.4 The lac repressor complex: A molecular machine......Page 37
2.2.1 Reaction kinetics......Page 40
2.2.2 Debye–Smoluchowski theory......Page 42
2.2.3 BWH theory......Page 44
2.2.4 Indirect read-out and induced fit......Page 46
3.1.1 Eukaryotic gene expression and Chromatin condensation......Page 48
3.1.2 A mathematical experiment and White’s theorem......Page 51
3.2 The worm-like chain......Page 54
3.2.2 Nucleosomes and the Marky–Manning transition......Page 56
3.2.3 Protein-DNA interaction under tension......Page 59
3.2.4 Force-Extension Curves......Page 61
3.3.1 Structural sequence sensitivity......Page 64
3.3.2 Thermal fluctuations......Page 66
4 Electrostatics in water and protein-DNA interaction......Page 67
4.1 Macro-ions and aqueous electrostatics......Page 68
4.2 The primitive model......Page 70
4.2.2 The primitive model: DH regime......Page 71
4.3.1 Charge renormalization......Page 72
4.3.2 Primitive model: Oosawa theory......Page 73
4.3.3 Primitive model: Free energy......Page 75
4.4.1 Counter-ion release......Page 77
4.4.2 Nucleosome formation and the isoelectric instability......Page 78
References......Page 81
Contents......Page 84
1 Introduction......Page 85
2 Cell motility and motor proteins......Page 86
3 Motility assays......Page 87
4 Single-molecules assays......Page 89
5 Atomic structures......Page 91
6 Proteins as machines......Page 92
7 Chemical forces......Page 94
8 Effect of force on chemical equilibria......Page 95
9 Effect of force on the rates of chemical reactions......Page 96
10 Absolute rate theories......Page 99
11 Role of thermal fluctuations in motor reactions......Page 101
12 A mechanochemical model for kinesin......Page 103
13 Conclusions and outlook......Page 106
Contents......Page 110
1.1 Motor proteins and Carnot engines......Page 112
1.2 Simple Brownian ratchet......Page 113
1.3 Polymerization ratchet......Page 114
1.4 Isothermal ratchets......Page 117
1.5 Motor proteins as isothermal ratchets......Page 118
1.6 Design principles for e.ective motors......Page 119
2.1 Swinging lever-arm model......Page 122
2.2 Mechano-chemical coupling......Page 124
2.3 Equivalent isothermal ratchet......Page 125
2.4 Many motors working together......Page 126
2.5 Designed to work......Page 129
2.6 Force-velocity relation......Page 130
2.7 Dynamical instability and biochemical synchronization......Page 132
3.1 Dynamical instabilities......Page 133
3.2 Bidirectional movement......Page 134
3.3 Critical behaviour......Page 135
3.4 Oscillations......Page 138
3.5 Dynamic buckling instability......Page 139
3.6 Undulation of flagella......Page 141
4.1 System performance......Page 143
4.2 Mechano-sensors: Hair bundles......Page 144
4.3 Active amplification......Page 145
4.4 Self-tuned criticality......Page 147
4.5 Motor-driven oscillations......Page 148
4.6 Channel compliance and relaxation oscillations......Page 150
4.7 Channel-driven oscillations......Page 152
4.8 Hearing at the noise limit......Page 153
Contents......Page 159
1.1 Introduction......Page 160
1.1.2 Biomolecular complexity and role for dynamic force spectroscopy......Page 161
1.1.3 Biochemical and mechanical perspectives of bond strength......Page 163
1.1.4 Relevant scales for length, force, energy, and time......Page 166
1.2 Brownian kinetics in condensed liquids: Old-time physics......Page 167
1.2.1 Two-state transitions in a liquid......Page 168
1.2.2 Kinetics of first-order reactions in solution......Page 169
1.3.1 Dissociation of a simple bond under force......Page 171
1.3.2 Dissociation of a complex bond under force: Stationary rate approximation......Page 172
1.3.3 Evolution of states in complex bonds......Page 176
1.4 Testing bond strength and the method of dynamic force spectroscopy......Page 177
1.4.1 Probe mechanics and bond loading dynamics......Page 178
1.4.2 Stochastic process of bond failure under rising force......Page 181
1.4.3 Distributions of bond lifetime and rupture force......Page 182
1.4.4 Crossover from near equilibrium to far from equilibrium unbonding......Page 185
1.4.5 Effect of soft-polymer linkages on dynamic strengths of bonds......Page 188
1.4.6 Failure of a complex bond and unexpected transitions in strength......Page 190
1.5 Summary......Page 198
References......Page 199
2.1 Hidden mechanics in detachment of multiple bonds......Page 200
2.2 Impact of cooperativity......Page 201
2.3.1 Markov sequence of random failures......Page 204
2.3.2 Multiple-complex bonds......Page 206
2.3.3 Multiple-ideal bonds......Page 207
2.3.4 Equivalent single-bond approximation......Page 208
2.4.2 Equivalent single-bond approximation......Page 211
2.5 Poisson statistics and bond formation......Page 212
2.6 Summary......Page 216
References......Page 217
Contents......Page 228
1 Introduction......Page 229
2.1 A little chemistry......Page 230
3.1 Motion in the laboratory frame......Page 232
3.2 Propulsion and steady velocity regimes......Page 233
3.3 Gel/bacterium friction and saltatory behaviour......Page 235
4.1 A spherical Listeria......Page 237
4.2 Spherical symmetry......Page 238
4.3 Steady state......Page 239
4.5 Symmetry breaking......Page 241
4.6 Limitations of the approach and possible improvements......Page 243
5 Conclusion......Page 246
References......Page 247
Contents......Page 250
1.1 The lipid/protein bilayer is a multicomponent smectic phase with mosaic like architecture......Page 251
1.2 The spectrin/actin cytoskeleton as hyperelastic cell stabilizer......Page 254
1.3 The actin cortex: Architecture and function......Page 257
2.1 Actin is a living semiflexible polymer......Page 261
2.2 Actin network as viscoelastic body......Page 265
2.3 Correlation between macroscopic viscoelasticity and molecular motional processes......Page 270
3.1 Manipulation of actin gels......Page 272
3.2 Control of organization and function of actin cortex by cell signalling......Page 277
4 Micromechanics and microrheometry of cells......Page 279
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 283
6 On cells as adaptive viscoplastic bodies......Page 286
7 Controll of cellular protrusions controlled by actin/myosin cortex......Page 290
References......Page 294
Contents......Page 298
1 Introduction......Page 299
2 Mimicking cell adhesion......Page 304
4 Soft shell adhesion is controlled by a double well interfacial potential......Page 306
5 How is adhesion controlled by membrane elasticity?......Page 309
6 Measurement of adhesion strength by interferometric contour analysis......Page 311
8 Measurement of unbinding forces, receptor-ligand leverage and a new role for stress fibers......Page 312
10 Conclusions......Page 315
A Appendix: Generic interfacial forces......Page 316
References......Page 320
Contents......Page 323
1 Why micro/nanofabrication?......Page 325
1 Introduction: The need to control flows in 2 1/2 D......Page 329
2 Somewhat simple hydrodynamics in 2 1/2 D......Page 331
3 The N-port injector idea......Page 338
References......Page 343
1 Introduction......Page 345
2.1 Fabrication......Page 347
2.4 DNA samples......Page 348
3.1 Basic results and dielectrophoretic force extraction......Page 349
4 Data and analysis......Page 353
5 Origin of the low frequency dielectrophoretic force in DNA......Page 357
6 Conclusion......Page 363
References......Page 364
1 Introduction......Page 366
2 Experimental approach......Page 370
3 Conclusions......Page 374
References......Page 375
2 Design......Page 376
3 Results......Page 377
4 Conclusions......Page 382
References......Page 383
1 The problems with insulators in rachets......Page 384
2 An experimental test......Page 385
References......Page 391
1 Introduction......Page 392
2 The nearfield scanner......Page 393
3 The chip......Page 394
4 Experiments with molecules......Page 397
References......Page 401
2 Blood specifics......Page 402
3 Magnetic separation......Page 407
4 Microfabrication......Page 408
5 Magnetic field gradients......Page 409
6 Device interface......Page 411
7 A preliminary blood cell run......Page 416
8 Conclusions......Page 419
References......Page 420
1 Introduction......Page 421
2 Technology......Page 422
3 Experiments......Page 425
References......Page 428
Contents......Page 431
1 Introduction......Page 432
2 New technologies......Page 434
3 Sequence comparison......Page 436
4 Clustering......Page 439
5 Gene regulation......Page 441
References......Page 442
Contents......Page 445
1 Enzymatic networks. Proofreading knots: How DNA topoisomerases disentangle DNA......Page 447
1.1 Length scales and energy scales......Page 448
1.2 DNA topology......Page 449
1.3 Topoisomerases......Page 450
1.4 Knots and supercoils......Page 453
1.5 Topological equilibrium......Page 455
1.6 Can topoisomerases recognize topology?......Page 456
1.7 Proposal: Kinetic proofreading......Page 457
1.8 How to do it twice......Page 458
1.9 The care and proofreading of knots......Page 460
1.10 Suppression of supercoils......Page 462
1.11 Problems and outlook......Page 464
2.1 The regulation of gene expression......Page 466
2.2 Gene expression arrays......Page 469
2.3 Analysis of array data......Page 472
2.4 Some simplifying assumptions......Page 473
2.5 Probeset analysis......Page 475
2.6 Discussion......Page 479
3 Neural and gene expression networks: Song-induced gene expression in the canary brain......Page 480
3.1 The study of songbirds......Page 481
3.2 Canary song......Page 482
3.3 ZENK......Page 483
3.5 Histological analysis......Page 485
3.6 Natural vs. artificial......Page 488
3.7 The Blush II: gAP......Page 489
3.8 Meditation......Page 490
References......Page 491
Contents......Page 494
1 Introduction......Page 495
2 Photon counting......Page 499
3 Optimal performance at more complex tasks......Page 509
4 Toward a general principle?......Page 526
5 Learning and complexity......Page 546
6 A little bit about molecules......Page 560
7 Speculative thoughts about the hard problems......Page 572
References......Page 581