Mechanics of Motor Proteins and the Cytoskeleton
by Jonathon Howard
Contents (partly abridged)

1 Introduction

2 Mechanical Forces
Force; single-molecule level
Motion of Springs, Dashpots, and Masses Induced by Applied Forces ;
bacterial motor
Motion of Combinations of Mechanical Elements; bacterial inertia, proteins,
chemical bonds
Motion of a Mass and Spring with Damping; motor proteins
Work, Energy, and Heat; chemical bonds, protein conformations
Summary: Generalizations to More Complex Mechanical Systems
3 Mass, Stiffness, and Damping of Proteins
Mass; Elasticity; tension rod, springs
The Molecular Basis of Elasticity; solids
Viscous Damping; jar of honey
The Molecular Basis of Viscosity
The Global Motions of Proteins are Overdamped; ribosome
The Motions of the Cytoskeleton and Cells Are Also Overdamped
Summary; Problems
4 Thermal Forces and Diffusion
Boltzmann's Law; applications
Equipartition of Energy
Diffusion as a Random Walk
Einstein Relation; diffusion of ions
Some Solutions to the Diffusion Equation; Point Source; First-Passage Times
Correlation Times*; free and tethered proteins
Fourier Analysis*; power spectrum
The Magnitude of the Thermal Force*; electrical circuits
Summary; Problems
*An asterisk denotes a more advanced section.
5 Chemical Forces
Chemical Equilibria
The Effect of Force on Chemical Equilibria; ion channels in hair cells
Rate Theories of Chemical Reactions
Effect of Force on Chemical Rate Constants; ratchet models for motor proteins;
unfolding titin
Bimolecular Reactions: association rates; Michaelis-Menten equation;
protein complexes
Cyclic Reactions and Free Energy Transduction
Summary; Problems
6 Polymer Mechanics
Flexural Rigidity and the Beam Equation
Applications of the Beam Equation: Bending and Buckling; cantilever, glass
fibers; microtubules, coiled coil; buckling; force required for a microtubule
Drag Forces on Slender Rods; sperm; gliding assays
Dynamics of Bending and Buckling; relaxation of MTs and action filaments;
time constant of a force fiber
Thermal Bending of Filaments: persistence length, semiflexible polymers,
entropic elasticity, spring constant of a freely jointed chain, worm-like chain

7 Structures of Cytoskeletal Filaments
Structures of the Subunits
Families of Cytoskeletal Proteins: Actin, Tubulin,

Intermediate Filament Proteins
Filament Structures: Actin Filament, Microtubule, Coiled Coils,
Intermediate Filaments
Summary: Structural Basis for the Length, Strength, Straightness, and Polarity
of Filaments
8 Mechanics of the Cytoskeleton
Rigidity of Filaments in Vivo: Actin in Muscle, in Sterocilia, Microtubules in
Sperm, Keratin-Containing Materials
Rigidity of Filaments in Vitro: Actin, Microtubules, Coiled Coils,
Intermediate Filaments, Bacterial Flagella, DNA and Titin
Summary: Material Properties of Cytoskeletal Proteins
9 Polymerization of Cytoskeletal Filaments
Passive Polymerization: The Equilibrium Polymer
Single-Stranded Filaments Are Short
Multistranded Filaments Grow and Shrink at Their Ends
Other Properties of Multistranded Filaments
Binding Energies and the Loss of Entropy
Structure and Dimensionality
Summary; Problems
10 Force Generation by Cytoskeletal Filaments
Generation of force by Polymerization and Depolymerization in Vivo
Generation of Force in Vitro
Equilibrium Force
Brownian Ratchet Model: Reaction-Limited Polymerization, Diffusion-Limited
Examples of Motility Driven by Actin Polymerization; listeria, in
sea cucumber sperm
Other Kinetic Models; Summary
11 Active Polymerization
Actin and Tubulin Hydrolysis Cycles
Filament Polarity, Treadmilling, and Nucleation
Dynamic Instability; switching between growth and shrinkage, GTP-cap model
Work during Polymerization and Depolymerization
Structural Changes Attending Nucleotide Hydrolysis

PART III Motor Proteins

12 Structures of Motor Proteins
Crossbridges and the Domain Organization of Motor Proteins
Motor Families
High-Resolution Structures
Docking of Motors to Their Filaments

13 Speeds of Motors
The Speeds of Motors in Vivo
Rowers and Porters
In Vitro Motility Assays
Processive and Nonprocessive Motors
The Hydrolysis Cycle and the Duty Ratio
Analogies to Internal Combustion Machines and Animal Locomotion
Summary: Adaptation to Function

14 ATP Hydrolysis
ATP: adenosine triphosphate
Coupling Chemical Changes to Conformational Changes
Hydrolysis of ATP by Skeletal Muscle Mysosin: Without and with action
Hydrolysis of ATP by Conventional Kinesin: Without and with microtubles;
head coordination.
Functional Differences between Kinesin and Myosin ATPase Cycles: Kinesin is
attached during its rate limiting step, but myosin is detached;
Biochemical evidence for kinesin's processivity, that Mysosin has a low
duty ratio
15 Steps and Forces
Distances that Characterize a Motor Reaction
Single-Motor Techniques: forces; displacements; sensitivity of a
photodetector; calibration, single-molecule fluorescence
Steps, Paths, and Force: Conventional Kinesin; Myosin II; Other Motors
The Structural Basis for the Duty Ratio
16 Motility Models: From Crossbridges to Motion
Macroscopic and Microscopic Descriptions of Motility
Powerstroke Model
Role of Thermal Fluctuations in the Power Stroke
Crossbridge Model for Muscle Contraction
Comparison of the Model to Muscle Data: Force-Velocity Curve and Efficiency;
Transients; Powerstroke, Path Distance and Duty Ratio; One step per ATP
A Crossbridge Model for Kinesin
Summary: Comparison between Motile Systems


Appendices: (see selected contents list below)