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Lang, Matthew, and Roger D. Kamm, 2.797J Molecular, Cellular, and Tissue Biomechanics, Fall 2006. (Massachusetts Institute of Technology: MIT OpenCourseWare), http://ocw.mit.edu (Accessed 07 Jul, 2010). License: Creative Commons BY-NC-SA
The focal adhesion complex. (Figure by MIT OCW.)
Course Highlights
This course features slides and notes by both the professors and TAs in the lecture notes and recitations sections.
Course Description
This course develops and applies scaling laws and the methods of continuum mechanics to biomechanical phenomena over a range of length scales. Topics include structure of tissues and the molecular basis for macroscopic properties; chemical and electrical effects on mechanical behavior; cell mechanics, motility and adhesion; biomembranes; biomolecular mechanics and molecular motors. The class also examines experimental methods for probing structures at the tissue, cellular, and molecular levels.
Syllabus
Course Objectives
This course develops and applies scaling laws and the methods of continuum mechanics to biomechanical phenomena over a range of length scales, from molecular to cellular to tissue or organ level. It is intended for undergraduate students who have taken a course in differential equations and an introductory course in molecular biology. In addition, some background in either statistical or classical thermodynamics is useful. Prerequisites: 18.03 or 3.016; 7.012; 2.370 or 2.772. Topics include:
Molecular Mechanics
Mechanics at the nanoscale: Intermolecular forces and their origins; Single molecules; Thermodynamics and statistical mechanics; Formation and dissolution of bonds: Mechanochemistry; Motion at the molecular and macromolecular level; Muscle mechanics; Experimental methods at the single molecule level - optical and magnetic traps, force spectroscopy, light scattering.
Tissue Mechanics
Elastic (time independent), viscoelastic and poroelastic (time-dependent) behavior of tissues; Continuum and microstructural models, Constitutive laws, electromechanical and physicochemical properties of tissues; Physical regulation of cellular metabolism; Experimental methods - macroscopic rheology.
Cellular Mechanics
Static and dynamic cell processes; Cell migration; Mechanics of biomembranes; The cytoskeleton and cortex; Microrheological properties and their implications; Mechanotransduction; Experimental methods - passive and active rheology.
Textbooks and Reference Materials
Most of the material will come from journal articles and notes to be handed out by the instructors.
Texts in the library that are useful as general references include:
 Fung, Y. C. Biomechanics: Mechanical Properties of Living Tissues. 2nd ed. New York, NY: Springer-Verlag, 1993. ISBN: 9780387979472.
Boal, David H. Mechanics of the Cell. New York, NY: Cambridge University Press, 2002. ISBN: 9780521792585.
Lodish, Harvey F. Molecular Cell Biology. New York, NY: W. H. Freeman and Co., 2003. ISBN: 9780716743668.
Dill, Ken A., and Sarina Bromberg. Molecular Driving Forces. New York, NY: Garland Science, 2002. ISBN: 9780815320517.
Howard, Jonathon. Mechanics of Motor Proteins and the Cytoskeleton. Sunderland, MA: Sinauer Associates, 2001. ISBN: 9780878933341.
Mofrad, Mohammad R. K., and Roger D., Kamm. Cytoskeletal Mechanics: Models and Measurements. New York, NY: Cambridge University Press, 2006. ISBN: 9780521846370.
Course Structure and Assignments
20.310/2.797/6.024 will be taught in lecture format, but with liberal use of class examples to motivate the course material and link it with various biological issues. Readings will be drawn from a variety of primary and text sources as indicated in the attached lecture schedule. Problems will be assigned each week to be handed in and graded. There will be two in-class exams and a term paper due at the end of the term (details to be described in class).
A term paper will be assigned that will require you to delve more deeply into one of the topics of the course. Additional information concerning the term paper will be provided at a later date.
Grading
The term grade will be a weighted average of exams, term paper and homework grades. The weighting distribution will be:
Grading criteria.
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ACTIVITIES
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PERCENTAGES
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Two Quizzes
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60%
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Term Paper
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20%
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Homeworks
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20%
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Homework grading is intended to show you how well you are progressing in learning the course material. You are encouraged to seek advice or help from other students and/or to work in study groups. However, the work that is turned in must be your own. The homework exercise should be viewed as a learning experience, not a competition.
The Term Paper is meant to be an individual effort. However, you should feel free to discuss your project with fellow students. The report is to be written entirely by you. You should acknowledge other sources with proper citations.
Calendar
Course calendar.
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LEC #
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TOPICS
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LECTURERS
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1
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Introduction: From Tissue Biomechanics to Molecular Nanomechanics, and Biomechanical Scaling
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Kamm/Lang
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Molecular Mechanics Introduction
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2
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Length, Time and Energy Scales in Biology
kT as ruler of molecular forces thermal forces and Brownian motion life at low Re.
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Lang
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3
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Molecules of Interest: DNA, Proteins, Actin, Peptides, Lipids and Molecular-level Forces
Molecular forces: charges, dipole, Van der Waals, hydrogen bonding etc.
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Lang
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4
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Random Walks, Diffusion, Life at Low Reynolds Number
Statistics of random walks, freely jointed chain, origins of elastic forces. Extreme extension of a FJC and modeling force as an effective potential field.
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Lang
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5
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Thermodynamics and Elementary Statistical Mechanics
Review of classical thermodynamics, entropy, equilibrium, open systems, ensembles, Boltzmann distribution, entropic forces.
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Lang
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6
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Reaction Coordinates, Energy Landscapes and Kinetics
Reaction coordinates and chemical equilibrium - Kramers / Eyring rate theories, effect of forces on chemical equilibrium.
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Lang
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7
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Experimental Tools for Pushing and Pulling on Molecules and Imaging
Intro to AFM, magnetic force, case study of an optical trap calibrations and measurement intro to fluorescence spectroscopy, force spectroscopy.
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Lang
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8
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Single Molecule Measurements and Introduction to Biological Motors
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Lang
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9
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Single Molecule Measurements and Biological Motors a Closer Look
Kinesin a closer look study, analysis methods, cycle models.
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Lang
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10
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Introduction to Polymerization Based Motility
Fiber microstructure - Actin and microtubule dynamics, methods of visualizing actin diffusion and polymerization - polymerization force Persistent Chain Model and Cooperativity The worm-like chain model, persistence length as a measure of rigidity.
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Lang
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Tissue Mechanics Introduction
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11
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Elastic (Time-Independent) Behavior of Tissues
Basic concepts of stress, elastic strain; stress-strain constitutive relations for tissues modeled using a Hookean constitutive law.
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Kamm
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Quiz 1 (in Class)
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12
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Elastic (Time-Independent) Behavior of Tissues (cont.)
Homogeneous/nonhomogeneous; isotropic/anisotropic; linear/nonlinear behavior of tissues. Relation between nano-molecular constituents and macroscopic tensile, compressive, and shear properties of connective tissues.
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Kamm
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13
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Composition and Nanomolecular Structure of Extracellular Matrix
Collagens, proteoglycans, elastin; Cellular synthesis and secretion of ECM macromolecules; Stress-strain characteristics of tissue; Examples using concepts of elasticity.
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Kamm
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14
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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).
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Kamm
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15
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Viscoelasticity (cont.)
Examples of viscoelastic behavior. Comparison of models to real measurements. Applications selected from among cartilage, vascular wall, actin gels.
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Kamm
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16
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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 bahavior.
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Kamm
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17
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Poroelastic (Time-Dependent ) Behavior of Tissues (cont.)
Examples: soft tissues in health and disease; e.g., cornea; arthritis and joint degeneration; isotropic cross-linked gels compared to fibrous tissues such as meniscus, cornea (relevant to corneal dystrophy), tendon, ligament, cartilage, bone.
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Kamm
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Cell Mechanics
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18
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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.
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Kamm
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19
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Biomembranes
Stiffness and role of transmembrane proteins - Equations for a 2-D elastic plate - Patch-clamp experiments - Membrane cortex - Vesicles: model systems.
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Kamm
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20
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The Cytoskeleton
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, biopolymer network.
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Kamm
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21
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Cell Machinery, Simple Models for Cell Migration and Motility
Measurement of cell motility (speed, persistence, "diffusivity") - Simple models for cell migration, - Actin filament assembly/crosslinking and disassembly.
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Lang
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22
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Mechanobiology (the "Mechanome")
Intracellular signaling relating to physical force - Molecular mechanisms of force transduction - Mechanotransduction, Force estimates and distribution of stresses within the cell.
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Kamm
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23
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Capstone Lecture 1
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24
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Capstone Lecture 2
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25
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Capstone Lecture 3
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26
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Capstone Lecture 4
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Final Exam (Quiz 2)
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Capstone Problems: Integration from Molecular to Cellular to Tissue
Depending on time, one or more of the following topics will be presented for discussion during the Capstone Lectures.
Molecular Electromechanics, Electromechanical and Physicochemical Properties of Tissues
Relation between molecular structure of ECM macromolecules and resulting macroscopic tissue function; Feedback between molecular, cellular, and tissue mechanics in vivo. Role of electrical and osmotic phenomena in determining tissue biomechanical behavior. Fluid convection of ions during tissue deformation and electrokinetic phenomena; electrostatic interactions between charged ECM molecules. Examples: bone, muscle, soft connective tissues; streaming potentials and electroosmosis; molecular electromechanical forces.
Physical Regulation of Cellular Metabolism: Tissue-level Deformation
Effects of mechanical forces and deformations on cell and tissue responses at the levels of transcription, translation, and post-translational modifications; relation between macroscopic tissue deformation and cell, cell-matrix deformations: cellular metabolic and biosynthetic responses. Current understanding of mechano-signal transduction. Examples: arterial endothelium, tendon, cartilage, bone.
Muscle Constriction from the Molecular to Macro Scale (Kamm)
Characteristics of contracting muscle - Hill's equation - Force-velocity curves - Muscle energetics, activation - Cross-bridge dynamics - Models for muscle behavior.
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