The Physics of Living Processes

Thomas Andrew Waigh School of Physics and Astronomy, Photon Science Institute, University of Manchester

Preface xiii Acknowledgements xvii I Building Blocks 1 1 Molecules 3 1.1 Chemical Bonds and Molecular Interactions 3 1.2 Chirality 7 1.3 Proteins 7 1.4 Lipids 15 1.5 Nucleic Acids 16 1.6 Carbohydrates 21 1.7 Water 24 1.8 Proteoglycans and Glycoproteins 25 1.9 Viruses 26 1.10 Other Molecules 28 Suggested Reading 28 Tutorial Questions 1 29 2 Cells 31 2.1 The First Cell 32 2.2 Metabolism 33 2.3 Central Dogma of Biology 34 2.4 Darwin s Theory of Natural Selection 38 2.5 Mutations and Cancer 40 2.6 Prokaryotic Cells 41 2.7 Eukaryotic Cells 41 2.8 Chromosomes 44 2.9 Cell Cycle 45 2.10 Genetic Code 45 2.11 Genetic Networks 45 2.12 Human Genome Project 47 2.13 Genetic Fingerprinting 49 2.14 Genetic Engineering 50 2.15 Tissues 51 2.16 Cells as Experimental Models 51 2.17 Stem Cells 52 Suggested Reading 53 Tutorial Questions 2 54 II Soft Condensed-Matter Techniques in Biology 55 3 Introduction to Statistics in Biology 57 3.1 Statistics 57 3.2 Entropy 60 3.3 Information 61 3.4 Free Energy 62 3.5 Partition Function 63 3.6 Conditional Probability 65 3.7 Networks 66 Suggested Reading 67 Tutorial Questions 3 67 4 Mesoscopic Forces 69 4.1 Cohesive Forces 69 4.2 Hydrogen Bonding 71 4.3 Electrostatics 73 4.3.1 Unscreened Electrostatic Interactions 73 4.3.2 Screened Electrostatic Interactions 74 4.3.3 The Force Between Charged Aqueous Spheres 77 4.4 Steric and Fluctuation Forces 79 4.5 Depletion Forces 82 4.6 Hydrodynamic Interactions 84 4.7 Bell s Equation 84 4.8 Direct Experimental Measurements 86 Suggested Reading 89 Tutorial Questions 4 89 5 Phase Transitions 91 5.1 The Basics 91 5.2 Helix Coil Transition 94 5.3 Globule Coil Transition 98 5.4 Crystallisation 101 5.5 Liquid Liquid Demixing (Phase Separation) 104 Suggested Reading 108 Tutorial Questions 5 109 6 Liquid Crystallinity 111 6.1 The Basics 111 6.2 Liquid Nematic Smectic Transitions 123 6.3 Defects 125 6.4 More Exotic Possibilities for Liquid-Crystalline Phases 130 Suggested Reading 132 Tutorial Questions 6 132 7 Motility 135 7.1 Diffusion 135 7.2 Low Reynolds Number Dynamics 142 7.3 Motility of Cells and Micro-Organisms 144 7.4 First-Passage Problem 148 7.5 Rate Theories of Chemical Reactions 152 7.6 Subdiffusion 153 Suggested Reading 155 Tutorial Questions 7 155 8 Aggregating Self-Assembly 157 8.1 Surface-Active Molecules (Surfactants) 160 8.2 Viruses 163 8.3 Self-Assembly of Proteins 167 8.4 Polymerisation of Cytoskeletal Filaments (Motility) 167 Suggested Reading 172 Tutorial Questions 8 172 9 Surface Phenomena 173 9.1 Surface Tension 173 9.2 Adhesion 175 9.3 Wetting 177 9.4 Capillarity 180 9.5 Experimental Techniques 183 9.6 Friction 184 9.7 Adsorption Kinetics 186 9.8 Other Physical Surface Phenomena 188 Suggested Reading 188 Tutorial Questions 9 188 10 Biomacromolecules 189 10.1 Flexibility of Macromolecules 189 10.2 Good/Bad Solvents and the Size of Flexible Polymers 198 10.3 Elasticity 203 10.4 Damped Motion of Soft Molecules 206 10.5 Dynamics of Polymer Chains 209 10.6 Topology of Polymer Chains Supercoiling 214 Suggested Reading 216 Tutorial Questions 10 217 11 Charged Ions and Polymers 219 11.1 Electrostatics 222 11.2 Deybe Huckel Theory 226 11.3 Ionic Radius 229 11.4 The Behaviour of Polyelectrolytes 232 11.5 Donnan Equilibria 234 11.6 Titration Curves 236 11.7 Poisson Boltzmann Theory for Cylindrical Charge Distributions 238 11.8 Charge Condensation 239 11.9 Other Polyelectrolyte Phenomena 243 Suggested Reading 244 Tutorial Questions 11 245 12 Membranes 247 12.1 Undulations 248 12.2 Bending Resistance 250 12.3 Elasticity 253 12.4 Intermembrane Forces 258 12.5 Passive/Active Transport 260 12.6 Vesicles 267 Suggested Reading 268 Tutorial Questions 12 268 13 Continuum Mechanics 269 13.1 Structural Mechanics 270 13.2 Composites 273 13.3 Foams 275 13.4 Fracture 277 13.5 Morphology 278 Suggested Reading 278 Tutorial Questions 13 279 14 Fluid Mechanics 281 14.1 Newton s Law of Viscosity 282 14.2 Navier Stokes Equations 282 14.3 Pipe Flow 283 14.4 Vascular Networks 285 14.5 Haemodynamics 285 14.6 Circulatory Systems 289 14.7 Lungs 289 Suggested Reading 291 Tutorial Questions 14 291 15 Rheology 293 15.1 Storage and Loss Moduli 295 15.2 Rheological Functions 298 15.3 Examples from Biology: Neutral Polymer Solutions, Polyelectrolytes, Gels, Colloids, Liquid Crystalline Polymers, Glasses, Microfluidics 299 15.3.1 Neutral Polymer Solutions 299 15.3.2 Polyelectrolytes 303 15.3.3 Gels 305 15.3.4 Colloids 309 15.3.5 Liquid-Crystalline Polymers 310 15.3.6 Glassy Materials 310 15.3.7 Microfluidics in Channels 312 15.4 Viscoelasticity of the Cell 312 Suggested Reading 314 Tutorial Questions 15 314 16 Motors 315 16.1 Self-Assembling Motility Polymerisation of Actin and Tubulin 317 16.2 Parallelised Linear Stepper Motors Striated Muscle 320 16.3 Rotatory Motors 325 16.4 Ratchet Models 327 16.5 Other Systems 329 Suggested Reading 329 Tutorial Questions 16 330 17 Structural Biomaterials 331 17.1 Cartilage Tough Shock Absorbers in Human Joints 331 17.2 Spider Silk 341 17.3 Elastin and Resilin 342 17.4 Bone 343 17.5 Adhesive Proteins 343 17.6 Nacre and Mineral Composites 345 Suggested Reading 346 Tutorial Questions 17 346 18 Phase Behaviour of DNA 347 18.1 Chromatin Naturally Packaged DNA Chains 347 18.2 DNA Compaction An Example of Polyelectrolyte Complexation 350 18.3 Facilitated Diffusion 351 Suggested Reading 354 III Experimental Techniques 355 19 Experimental Techniques 357 19.1 Mass Spectroscopy 357 19.2 Thermodynamics 359 19.2.1 Differential Scanning Calorimetry 360 19.2.2 Isothermal Titration Calorimetry 360 19.2.3 Surface Plasmon Resonance and Interferometry-Based Biosensors 360 19.3 Hydrodynamics 362 19.4 Optical Spectroscopy 363 19.4.1 Rayleigh Scattering 363 19.4.2 Brillouin Scattering 364 19.4.3 Terahertz/Microwave Spectroscopy 364 19.4.4 Infrared Spectroscopy 365 19.4.5 Raman Spectroscopy 366 19.4.6 Nonlinear Spectroscopy 367 19.4.7 Circular Dichroism and UV Spectroscopy 369 19.5 Optical Microscopy 369 19.5.1 Fluorescence Microscopy 376 19.5.2 Super-Resolution Microscopy 378 19.5.3 Nonlinear Microscopy 382 19.5.4 Polarisation Microscopy 382 19.5.5 Optical Coherence Tomography 382 19.5.6 Holographic Microscopy 383 19.5.7 Other Microscopy Techniques 383 19.6 Single-Molecule Detection 384 19.7 Single-Molecule Mechanics and Force Measurements 384 19.8 Electron Microscopy 395 19.9 Nuclear Magnetic Resonance Spectroscopy 396 19.10 Static Scattering Techniques 397 19.11 Dynamic Scattering Techniques 408 19.12 Osmotic Pressure 412 19.13 Chromatography 415 19.14 Electrophoresis 415 19.15 Sedimentation 420 19.16 Rheology 424 19.17 Tribology 431 19.18 Solid Mechanical Properties 432 Suggested Reading 432 Tutorial Questions 19 433 IV Systems Biology 437 20 Chemical Kinetics 439 20.1 Conservation Laws 440 20.2 Free Energy 440 20.3 Reaction Rates 441 20.4 Consecutive Reactions 449 20.5 Case I and II Reactions 450 20.6 Parallel Reactions 452 20.7 Approach to Chemical Equilibrium 453 20.8 Quasi-Steady-State Approximation 456 20.9 General Kinetic Equation Analysis 459 Suggested Reading 459 Tutorial Questions 20 460 21 Enzyme Kinetics 461 21.1 Michaelis Menten Kinetics 461 21.2 Lineweaver Burke Plot 465 21.3 Enzyme Inhibition 466 21.4 Competitive Inhibition 466 21.5 Allosteric Inhibition 467 21.6 Cooperativity 468 21.7 Hill Plot 470 21.8 Single Enzyme Molecules 470 Suggested Reading 472 Tutorial Questions 21 472 22 Introduction to Systems Biology 473 22.1 Integrative Model of the Cell 473 22.2 Transcription Networks 474 22.3 Gene Regulation 474 22.4 Lac Operon 477 22.5 Repressilator 479 22.6 Autoregulation 481 22.7 Network Motifs 483 22.8 Robustness 489 22.9 Morphogenesis 490 22.10 Kinetic Proofreading 492 22.11 Temporal Programs 493 22.12 Nonlinear Models 494 22.13 Population Dynamics 497 Suggested Reading 498 Tutorial Questions 22 499 V Spikes, Brains and the Senses 501 23 Spikes 503 23.1 Structure and Function of a Neuron 503 23.2 Membrane Potential 503 23.3 Ion Channels 506 23.4 Voltage Clamps and Patch Clamps 508 23.5 Nernst Equation 509 23.6 Electrical Circuit Model of a Cell Membrane 511 23.7 Cable Equation 513 23.8 Hodgkin Huxley Model 515 23.9 Action Potential 518 23.10 Spikes Travelling Electrical Waves 520 23.11 Cell Signalling 523 Suggested Reading 524 Tutorial Questions 23 525 24 Physiology of Cells and Organisms 527 24.1 Feedback Loops 528 24.2 Nonlinear Behaviour 533 24.3 Potential Outside an Axon 533 24.4 Electromechanical Properties of the Heart 535 24.5 Electrocardiogram 536 24.6 Electroencephalography 537 Suggested Reading 539 Tutorial Questions 24 540 25 The Senses 541 25.1 Biological Senses 541 25.2 Weber s Law 542 25.3 Information Processing and Hyperacuity 543 25.4 Mechanoreceptors 543 25.5 Chemoreceptors 545 25.6 Photoreceptors 549 25.7 Thermoreceptors 551 25.8 Electroreceptors 552 25.9 Magnetoreceptors 552 Suggested Reading 553 Tutorial Questions 25 554 26 Brains 555 26.1 Neural Encoding Inverse Problem 558 26.2 Memory 560 26.3 Motor Processes 564 26.4 Connectome 565 26.5 Cohesive Properties 566 Suggested Reading 567 Tutorial Questions 26 568 Appendix A: Physical Constants 569 Appendix B: Answers to Tutorial Questions 571 Index 593