Readings

These readings are presented in chronological order. The table below maps the readings to specific lecture sessions.

Suggested Readings

[GKM-Text] = Grodzinsky, A., R. Kamm, and L. Mahadevan. Molecular, Cell and Tissue Biomechanics. Draft of textbook in preparation, 2003.

Daune, Michel. Chapter 2 in Molecular Biophysics. New York, NY: Oxford University Press, 1999. ISBN: 9780198577836.

Dill, K. A., and S. Bromberg. Chapters 6, 8 and 10 in Molecular Driving Forces. New York, NY: Routledge, 2002. ISBN: 9780815320517.

Boal, David H. Chapter 2 in Mechanics of the Cell. Cambridge, UK: Cambridge University Press, 2002. ISBN: 9780521792585.

Stricka, Terence, Jean-Francois Allemanda, Vincent Croquettea, and David Bensimon. "Twisting and stretching single DNA molecules." Progress in Biophysics & Molecular Biology 74 (2002): 115-140.

Coccoa, Simona, John F. Markob, and Remi Monasson. "Theoretical Models for Single - Molecule DNA and RNA Experiments: from Elasticity to Unzipping." C. R. Physique 3 (2002): 569-584.

Liphardt, Jan, Bibiana Onoa, Steven B. Smith, Ignacio Tinoco Jr., and Carlos Bustamante. "Reversible Unfolding of Single RNA Molecules by Mechanical Force." Science 292 (April 2001): 733-737.

Howard, Johnathon. Chapters 5 and 10 in Mechanics of Motor Proteins and the Cytoskeleton. Sunderland, MA: Sinauer Associates, 2001. ISBN: 9780878933341.

Vale Ronald D., and Ronald A. Milligan. "The Way Things Move: Looking Under the Hood of Molecular Motor Proteins." Science 288 (April 2000): 88-95.

Mahadevan, L., and P. Matsudaira. "Motility Powered by Supramolecular Springs and Ratchets." Science 288 (April 2000): 95-99.

Ward, J. P. Solid Mechanics. New York, NY: Springer, 1992. ISBN: 9780792319498.

Lodish, H., et. al. Molecular Cell Biology. 3rd. ed. New York, NY: Scientific American Books/W.H. Freeman, 1995. ISBN: 9780716723806.

Malvern, Lawrence E. Chapter 6 in Introduction to the Mechanics of a Continuous Medium. Englewood Cliffs, N.J.: Prentice-Hall, 1969, pp. 278-282. ISBN: 134876032.

Fung, Y. C. Biomechanics: Mechanical Properties of Living Tissues. New York, NY: Springer-Verlag, 1993. ISBN: 9780387979472.

Ferry, J. D. "The Nature of Viscoelastic Behavior." Chapter 1 in Viscoelastic Properties of Polymers. New York, NY: Wiley, 1980. ISBN: 9780471048947.

Huang, Chun-Yuh, Michael A. Soltz, Monika Kopacz, Van C. Mow, and Gerard A. Ateshian. "Experimental Verification of the Roles of Intrinsic Matrix Viscoelasticity and Tension - Compression Nonlinearity in the Biphasic Response of Cartilage." Transactions of the ASME 125 (February 2003): 84-93.

Smita, Theo H., Jacques M. Huygheb, and Stephen C. Cowin. "Estimation of the Poroelastic Parameters of Cortical Bone." Journal of Biomechanics 35 (2002): 829-835.

Notes on Fiber Matrix Permeability. (PDF)

Kamm, R. "Derivation of the Viscous Flow Equations." 1999. (PDF)

Sonin, A. A. The Physical Basis of Dimensional Analysis. 2nd ed. (Self-published work.) MIT, 2001.

Stamenovic, D., and D. E. Ingber. "Models of Cytoskeletal Mechanics of Adherent Cells." Biomechan Model Mechanobiol. 1 (2002): 95-108.

Problem from Spring 2002: Oscillatory Compression of Poroelastic Tissue. (PDF)

Pollard Thomas D., and Gary G. Borisy. "Cellular Motility Driven by Assembly and Disassembly of Actin Filaments." Cell 112 (February 2003): 453-465.

Mogilner, Alex, and George Ostery. "Force Generation by Actin Polymerization II: The Elastic Ratchet and Tethered Filaments." Biophysical Journal 84 (March 2003): 1591-1605.

Orsello, Chase E., Douglas A. Lauffenburger, and Daniel A. Hammer. "Molecular Properties in Cell Adhesion: A Physical and Engineering Perspective." TRENDS in Biotechnology 19, no. 8 (August 2001): 310-316.

SES # TOPICS READINGS
L1 Introduction: From Tissue Biomechanics to Molecular Nanomechanics  
Molecular Mechanics
L2 Length, Time and Forces in Biology

Molecules of Interest: DNA, Proteins, Actin, Peptides, Lipids

Molecular Forces: Charges, Dipole, Van der Waals, Hydrogen Bonding

kT as Ruler of Molecular Forces

Thermal Forces and Brownian Motion

Life at Low Reynolds Number
Mahadevan, chapters on Molecular Mechanics from [GKM-Text].

Daune.

Dill, Chapter 6.
L3 Thermodynamics and Elementary Statistical Mechanics

Review of Classical Thermodynamics: Entropy, Equilibrium, Open Systems, Ensembles, Boltzmann Distribution, Entropic Forces
Dill, Chapter 8.
L4 Ideal Polymer Chains and Entropic Elasticity

Statistics of Random Walks - Freely Jointed Chain - Origins of Elastic Forces

Extreme Extension of a FJC and Modeling Force as an Effective Potential Field
Boal.

Mahadevan, chapters on Molecular Mechanics from [GKM-Text].

Journal articles.
L5 Persistent Chain Model and Cooperativity

The Worm-like Chain Model - Persistence Length as a Measure of Rigidity - Cooperativity Modeled using Ising Models

Examples: Actin Length Fluctuations, Pulling on DNA and Synthetic Polymers
Dill, Chapter 10.

Journal articles.
L6 Mechano-Chemistry

Reactions and Chemical Equilibrium - Kramers/Eyring Rate Theories - Effect of Forces on Chemical Equilibrium

Examples: Pulling on Titin, Bond Rupture Experiments
Howard, Chapter 5.

Journal articles.
L7 Motility at the Macromolecular Level

Forces by Polymerization - Concept of Equilibrium Force - Motor Proteins - Molecular Springs

Examples: Listeria, Acto-myosin Motors, Kinesin, Vorticellid
Howard, Chapter 10.

Journal articles.
L8 Linear Elasticity

Continuum Mechanics - Basis of Linear Elasticity: Stress, Strain vs. Strain-rate, Hooke's Law, Experiments to Measure the Moduli
Ward.
Tissue Mechanics
L9 Composition and Structure of the Extracellular Matrix (ECM)

Collagens, Proteoglycans, Elastin - Cellular Synthesis and Secretion of ECM Macromolecules - Cell-mediated Assembly of ECM
Lodish.

Journal articles.

Comper, W. D., ed. Extracellular Matrix. Collagen Superfamily, Proteoglycan Superfamily, and Elastin.
L10 Pushing and Pulling on Molecules

Guest Lecturer: Prof. Matt Lang
 
L11 Elastic (Time-Independent) Behavior of Tissues

Stress and Strain in Tissues Modeled via Hookian Constitutive Law - Homogeneous/NonHomogeneous - Isotropic/Anisotropic - Linear/Nonlinear Behavior of Tissues and Relation to the ECM - Relation between Molecular Constituents and Macroscopic Tensile, Compressive, and Shear Properties of Connective Tissues
 
L12 Examples

Isotropic Cross-linked Gels Compared to Fibrous Tissues such as Arterial Wall, Cornea (Relevant to Corneal Dystrophy), Tendon, Ligament, Cartilage, Bone, Lung
Fung.

Flory.

Grodzinsky, "Time Dependent Mechanical Behavior of Hydrated Biological Tissues," from [GKM-Text].

Journal articles.
L13 Viscoelastic (Time-Dependent) Behavior of Tissues

Time-dependent Viscoelastic Behavior of Tissues as Single-phase Materials - Transient Behavior (Creep and Stress Relaxation) - Dynamic Behavior (Storage and Loss Moduli) - Lumped Parameter Models (Advantages and Limitations)

Examples
Journal articles.

Ferry.

Fung.

Grodzinsky, "Time Dependent Mechanical Behavior of Hydrated Biological Tissues," from [GKM-Text].
L14 Viscoelastic (Time-Dependent) Behavior of Tissues (cont.)  
L15 Poroelastic (Time-Dependent) Behavior of Tissues

The Role of Fluid/Matrix Interactions in Tissue Biomechanics - Darcy's Law and Hydraulic Permeability, Continuity, Conservation of Momentum - Creep, Stress Relaxation, Dynamic Moduli Revisited - Poro-viscoelastic Behavior

Examples: Muscle and Soft Tissues in Health and Disease - e.g., Arthritis and Joint Degeneration
Journal articles.

Grodzinsky, "Time Dependent Mechanical Behavior of Hydrated Biological Tissues," from [GKM-Text].
E1 Midterm Quiz  
L16 Poroelastic (Time-Dependent) Behavior of Tissues (cont.)  
L17 Electromechanical and Physicochemical Properties of Tissues

Role of Electrical and Chemical Phenomena in Determining Tissue Biomechanical Behavior - Fluid Convection of Ions During Tissue Deformation and the Resulting "Electrokinetic" Phenomena - Electrostatic Interactions between Charged ECM

Molecules: Tissue Swelling and Donnan Osmotic Swelling Pressure

Examples: Bone, Muscle, Soft Connective Tissues -- Streaming Potentials and Electro-osmosis -- Tissue Swelling and Molecular Electromechanical Forces
Journal articles.

Grodzinsky, "Time Dependent Mechanical Behavior of Hydrated Biological Tissues," from [GKM-Text].
L18 Muscle Constriction From the Molecular to Macro Scale

Characteristics of Contracting Muscle - Hill's Equation - Force-velocity Curves - Muscle Energetics, Activation - Cross-bridge Dynamics - Models for Muscle Behavior
Kamm, chapters on Cell Mechanics from [GKM-text].
Cell Mechanics
L19 Structure of the Cell

Cellular Anatomy, Cytoskeleton, Membrane, Types of Attachment to Neighboring Cells or the ECM, Receptors, Different Cell Types, Experimental Measurements of Mechanical Behavior
 Lodish.
L20 Biomembranes

Stiffness and Role of Transmembrane Proteins - Equations for a 2-D Elastic Plate - Patch-clamp Experiments - Membrane Cortex - Vesicles: Model Systems
Kamm, chapters on Cell Mechanics from [GKM-text].

Journal articles.
L21 The Cytoskeleton

Fiber Microstructure - Actin and Microtubule Dynamics, Methods of Visualizing Actin Diffusion and Polymerization - Rheology of the Cytoskeleton - Active and Passive Measures of Deformation - Storage and Loss Moduli and their Measurements - Models of the Cytoskeleton: Continuum, Microstructural - Tensegrity, Cellular Solids, Polymer Solution
Lodish.

Kamm, chapters on Cell Mechanics from [GKM-text].
L22 Cell Peeking and Poking

Guest Lecturer: Prof. Peter So
 
L23 The Cytoskeleton (cont.)  
L24 Cell Adhesion and Aggregation

Cell Adhesion Assays, Cell-free Adhesion Assays - Receptor-ligand Interactions Mediated by the Cytoskeleton and the Cell Membrane - Focal Adhesions
Kamm, chapters on Cell Mechanics from [GKM-text].

Journal articles.
L25/E2 Cell Migration and Mechanotransduction

Measurement of Cell Motility (Speed, Persistence, "Diffusivity") - Simple Models for Cell Migration - Actin Filament Assembly/Crosslinking and Disassembly - Intracellular Signaling Relating to Physical Force - Molecular Mechanisms of Force Transduction - Force Estimates and Distribution within the Cell
Kamm, chapters on Cell Mechanics from [GKM-text].

Orsello.