Molecular, Cellular and Tissue Biomechanics (BE.410J)

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.