Forces, Machines and Signals

The Physics of Living Matter in 20 chapters — from “Numbers and noise in a small system” to “Genetic circuits and biological pattern”.

Chapters

  1. Numbers and noise in a small system
    • The first pass over biological physics
    • Poisson copy number in one cell
    • Relative fluctuation and the root-N rule
    • Binomial partitioning at cell division
    • Thermal force scale and equipartition noise
    • Biological dimensionless groups
    • Counting-limit estimate for a concentration
    • Relative fluctuation and equipartition noise, settled and open
    • Poisson copy number of the regulator, answered
    • Problems
  2. Diffusion: friction, capture and the crowded cytoplasm
    • Diffusion in the first pass over biological physics
    • The Einstein relation from sedimentation
    • The Langevin equation and the ballistic crossover
    • Diffusion equation solutions for release and step
    • The Smoluchowski rate for meeting molecules
    • Receptor patch capture on a cell
    • Drift-diffusion under a steady force
    • Facilitated search for a site on DNA
    • Anomalous subdiffusion and measuring D in cells
    • The Einstein relation and drift-diffusion, settled and open
    • The Einstein relation and GFP in cytoplasm
    • Problems
  3. Free energy at work: states, weights and entropic forces
    • From counting to the partition function
    • States and weights
    • Free energy of a state
    • The mass-action constant and binding
    • Two-state stability of a protein
    • Entropic force and osmotic pressure
    • The depletion force
    • Free-energy transduction by coupled reactions
    • States, weights and entropic force, settled and open
    • Problems
  4. Life at low Reynolds number
    • Coasting in the Stokes limit
    • Stokes flow and its drag laws
    • Reversibility and the scallop theorem
    • Drag anisotropy of a rod
    • Helical propulsion of a bacterium
    • Swimming power and the motor
    • Drag anisotropy in flagellar waves
    • Run-and-tumble motility
    • Why swim at all
    • Problems
  5. The elastic polymer: DNA from random walk to worm-like chain
    • The freely jointed chain in three dimensions
    • Rod bending and persistence length
    • The worm-like chain
    • Stretching the worm-like chain
    • Stretch and overstretch of DNA
    • Flory swelling of real chains
    • Genome packaging
    • Unfolded protein as polymer
    • Problems
  6. Cooperativity: zippers, melting and allosteric binding
    • Coupling and the all-or-none limit
    • The Zimm-Bragg helix-coil transition
    • DNA melting
    • Haemoglobin and the Hill function
    • Two conformations and the MWC model
    • Force-tilted equilibrium
    • Problems
  7. Charges in salt water and the assembly of amphiphiles
    • Water and the Bjerrum length
    • The Poisson-Boltzmann equation
    • Debye screening
    • The Gouy-Chapman layer at a membrane
    • Manning condensation on DNA
    • Counterion release and salt-dependent binding
    • The hydrophobic effect
    • Self-assembly and the critical micelle concentration
    • The packing parameter and aggregate shape
    • Debye screening at the lipid bilayer
    • Problems
  8. The fluid membrane: bending, flicker and shape
    • Membrane moduli of a two-dimensional fluid
    • Lysis tension and area strain
    • The Helfrich energy
    • κ from stretch in two monolayers
    • Budding cost and coat proteins
    • The undulation spectrum
    • Hidden area and entropic tension
    • Vesicle shapes and the red cell
    • Membrane diffusion in two dimensions
    • Membrane diffusion and the fluid sheet
    • Problems
  9. Filaments, networks and the mechanics of whole cells
    • Cytoskeletal stiffness of three filaments
    • Thermal contour analysis
    • Euler buckling in buffer and in cells
    • Polymerisation kinetics at filament ends
    • The Brownian ratchet
    • Dynamic instability
    • Network elasticity
    • Viscoelasticity and creep
    • Whole-cell mechanics
    • Whole-cell mechanics from filament parts
    • Problems
  10. Seeing molecules: diffraction, cryo-electron microscopy and fluorescence
    • Wavelengths and radiation damage
    • Scattering as a Fourier transform
    • Crystal diffraction resolution
    • The phase problem
    • Helical diffraction and DNA
    • The radiation damage limit
    • The point-spread function
    • The phase contrast CTF
    • Single-particle averaging
    • Molecular absorption and fluorescence
    • The FRET ruler
    • Localisation precision
    • Methods and the radiation damage limit
    • Problems
  11. Enzymes and molecular motors
    • Motors and the thermal force scale
    • The activation barrier rate
    • Michaelis-Menten kinetics
    • The force-dependent rate
    • Chemomechanical coupling and efficiency
    • Kinesin stepping
    • The Brownian ratchet motor
    • Duty ratio and muscle
    • Rotary motors
    • Kinesin stepping, efficiency and direction
    • Problems
  12. Measuring one molecule: traps, tweezers and single-molecule fluorescence
    • Single-molecule instruments and thermal noise
    • The optical gradient force
    • The optical trap force
    • The trap power spectrum
    • Step detection below the noise
    • Magnetic tweezers
    • The AFM force probe
    • Dynamic force spectroscopy
    • Single-fluorophore detection
    • smFRET dynamics and conformational states
    • Step detection and instrument limits
    • Problems
  13. Channels, pumps and the resting potential
    • The Nernst-Planck equation
    • Resting potential from the GHK equation
    • The Donnan equilibrium of trapped charges
    • The pump-leak steady state
    • Single-channel records and noise
    • Channel selectivity in the potassium filter
    • Voltage gating as a two-state tilt
    • Mechanosensitive gating by tension
    • Coupled transport by symporters
    • Open questions in channel selectivity
    • Problems
  14. Proton gradients, ATP synthesis and photosynthesis
    • Redox free energy
    • Chemiosmotic coupling
    • The proton-motive force
    • ATP synthase stoichiometry
    • The proton circuit
    • From photon to chemistry
    • The light-harvesting antenna
    • Photosynthetic efficiency
    • The status of chemiosmotic coupling
    • Problems
  15. The nerve impulse
    • The axon and the cable equation
    • Passive decay along an axon
    • The Hodgkin-Huxley conductances
    • Phase-plane analysis
    • Threshold in the excitability phase plane
    • Conduction velocity and diameter
    • Myelin and saltatory conduction
    • The impulse energy cost
    • Quantal release at the synapse
    • The status of the Hodgkin-Huxley model
    • Problems
  16. Muscle, heart and the fields outside the body
    • Impulse, muscle and volume conductor
    • Excitation-contraction coupling
    • The cardiac action potential
    • The body as a volume conductor
    • The Einthoven ECG
    • Biomagnetic fields of heart and brain
    • SQUID magnetometry
    • The inverse problem
    • Problems
  17. Hearing: from air pressure to a gated channel
    • Sound intensity from threshold to pain
    • The hearing threshold
    • The middle-ear transformer
    • Ear-canal resonance
    • Cochlear tonotopy
    • Hair-cell gating
    • The hearing noise limit
    • The cochlear amplifier
    • Problems
  18. Vision and photoreception: counting photons
    • Counting the photons of a faint star
    • Eye optics, briefly
    • Acuity, diffraction, sampling
    • Frequency of seeing
    • Rhodopsin isomerisation
    • The single-photon response
    • The dark noise limit
    • Trichromacy and univariance
    • Visual adaptation over nine decades
    • Problems
  19. Bones, blood and body size
    • Hip loads and beam bending
    • Bone bending and the hollow femur
    • Elastic similarity of bones
    • Pulsing flow and the Womersley number
    • Pulse-wave velocity in elastic arteries
    • The windkessel as an arterial capacitor
    • Murray's law of branching
    • Size and locomotion in jumping
    • Metabolic scaling explanations
    • Problems
  20. Genetic circuits and biological pattern
    • The promoter thermodynamic model
    • Hill regulation of genes
    • Expression kinetics and response time
    • Negative autoregulation
    • Toggle bistability and memory
    • Repressilator oscillation
    • Expression noise
    • The morphogen gradient
    • Turing instability
    • Problems