This is an archived course. A more recent version may be available at ocw.mit.edu.

Calendar

LEC # TOPICS LECTURERS
1 Introduction: From Tissue Biomechanics to Molecular Nanomechanics, and Biomechanical Scaling Kamm/Lang
Molecular Mechanics Introduction
2

Length, Time and Energy Scales in Biology

kT as ruler of molecular forces thermal forces and Brownian motion life at low Re.

 Lang
3

Molecules of Interest: DNA, Proteins, Actin, Peptides, Lipids and Molecular-level Forces

Molecular forces: charges, dipole, Van der Waals, hydrogen bonding etc.

 Lang
4

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.

 Lang
5

Thermodynamics and Elementary Statistical Mechanics

Review of classical thermodynamics, entropy, equilibrium, open systems, ensembles, Boltzmann distribution, entropic forces.

 Lang
6

Reaction Coordinates, Energy Landscapes and Kinetics

Reaction coordinates and chemical equilibrium - Kramers / Eyring rate theories, effect of forces on chemical equilibrium.

 Lang
7

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.

 Lang
8 Single Molecule Measurements and Introduction to Biological Motors Lang
9

Single Molecule Measurements and Biological Motors a Closer Look

Kinesin a closer look study, analysis methods, cycle models.

 Lang
10

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.

 Lang
Tissue Mechanics Introduction
11

Elastic (Time-Independent) Behavior of Tissues

Basic concepts of stress, elastic strain; stress-strain constitutive relations for tissues modeled using a Hookean constitutive law.

 Kamm
  Quiz 1 (in Class)  
12

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.

 Kamm
13

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.

 Kamm
14

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).

 Kamm
15

Viscoelasticity (cont.)

Examples of viscoelastic behavior. Comparison of models to real measurements. Applications selected from among cartilage, vascular wall, actin gels.

 Kamm
16

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.

 Kamm
17

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.

 Kamm
Cell Mechanics
18

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.

 Kamm
19

Biomembranes

Stiffness and role of transmembrane proteins - Equations for a 2-D elastic plate - Patch-clamp experiments - Membrane cortex - Vesicles: model systems.

 Kamm
20

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.

 Kamm
21

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.

 Lang
22

Mechanobiology (the "Mechanome")

Intracellular signaling relating to physical force - Molecular mechanisms of force transduction - Mechanotransduction, Force estimates and distribution of stresses within the cell.

 Kamm
23 Capstone Lecture 1  
24 Capstone Lecture 2  
25 Capstone Lecture 3  
26 Capstone Lecture 4  
  Final Exam (Quiz 2)  

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.