lecture01_kamm

lecture01_kamm - Molecular, Cellular & Tissue...

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Unformatted text preview: Molecular, Cellular & Tissue Biomechanics Matthew Lang (BE & ME), Roger Kamm (BE & ME) TA’s: Karolina Corin and Andrea Bryan Goal: Develop a fundamental understanding of biomechanics over a wide range of length scales. MOLECULAR MECHANICS Biomolecules and intermolecular forces Single molecule biopolymer mechanics Formation and dissolution of bonds Motion at the molecular/macromolecular level TISSUE MECHANICS Molecular structure --> physical properties Continuum, elastic models (stress, strain, constitutive laws) Viscoelasticity Poroelasticity Electrochemical effects on tissue properties CELLULAR MECHANICS Structure/function/properties of the cell Biomembranes The cytoskeleton Cell adhesion and aggregation Cell migration Mechanotransduction Some Learning Objectives 1. To understand the fundamental concepts of mechanics and be able to apply them to simple problems in the deformation of continuous media 2. To understand the underlying basis for the mechanical properties of molecules, cells and tissues 3. To be able to model biological materials using methods appropriate over diverse length scales 4. To be familiar with the wide spectrum of measurement techniques that are currently used to determine mechanical properties 5. To appreciate the close interconnections between mechanics and biology/chemistry of living systems Modeling Complex Material Properties Continuum Microstructural entangled polymer bending plate Constitutive relations and force balance Viscoelastic or poroelastic solid  21( t) strut model Figure by MIT OCW. Biomechanics at all length scales Traditional domain of biomechanics Quantum Molecular mechanics dynamics Networks and Large-scale, Continuum Brownian discrete or mechanics dynamics lumped systems Bone Cartilage Molecular motors Cytoskeletal rheology Swimming Cardiovascular system Gain analysis Migration Mechanotransduction Flight atoms 10-10 proteins 10-9 organelles 10-6 cells 10-2 organs organisms 100 meters Muscles: Spanning from Macro to Nano Figure by MIT OCW. Figure by MIT OCW. Typical Eukaryotic Cell Figure by MIT OCW. 1 µm = 10-6 m 1 nm = 10-9 m 1 Å = 10-10m Plasma Membrane Plasma Membrane 2-D Elastic Plate Figure by MIT OCW. Figure by MIT OCW. Cytoskeleton TEM image of a cytoskeleton removed due to copyright restrictions. “rigidity” Figure by MIT OCW. actin Diameter (nm) 6-8 Persistence Length (µm) 15 microtubule 10 60,000 intermediate filament 20-25 1-3 TEM image of a cytoskeleton removed due to copyright restrictions. TEM of cytoskeleton, Hartwick, http://expmed.bwh .harvard.edu When stressed, cells form stress fibers, mediated by a variety of actin-binding proteins. Actin filament: a force of 10 pN supported by a single actin filament (E~109 Pa) stretches by only 0.02%!! Diagram showing the structure of actin removed due to copyright restrictions. Measuring Complex Material Properties Aspiration Cell Poking Images removed due to copyright restrictions. T. Savin, MIT Cell Adhesion Physical forces effect bond association/dissociation Finite contact times Cell deformation Figure by MIT OCW. Dynamic Processes: Cell Migration Cell Motility Fluorescently marked actin Images removed due to copyright restrictions. • Actin is a polymer that contributes to the stiffness of the cytoskeleton • The cytoskeleton is active • Coordinated processes: adhesion, (de-) polymerization Active Cell Contraction Image removed due to copyright restrictions. Cardiac myocyte (Jan Lammerding) Cytoskeletal Mechanics Probed by External Force Image removed due to copyright restrictions. Fibroblast with fluorescent mitochondria forced by a magnetic bead D. Ingber, P. LeDuc Mechanotransduction: Hair cell stimulation tip link tension in tip link increases stereocilium Image removed due to copyright restrictions. SEM of the stereocilia on the surface of a single hair cell (Hudspeth) Tension in the tip link activates a stretch-activated ion channel, leading to intracellular calcium ion fluctuations. Image removed due to copyright restrictions. Molecular dynamics simulation of channel regulation by membrane tension (Gullingsgrud, et al., Biophys J, 2001) 10 o pore radius (A) 15 With membrane tension 5 0 Initial configuration -40 -20 0 20 40 o coordinate along pore (A) But other evidence suggests that the pore increases to >20 angstroms! Figure by MIT OCW. Figure by MIT OCW. Molecular, Cellular & Tissue Biomechanics Biology is soft, wet & dynamic Using Engineering/Physics to Unravel & Manipulate Biology • Scaling arguments • Mechanical models • Experimental techniques • Importance of the stochastic nature of biology Further Information Suggested Readings: (a) Y. C. Fung, Biomechanics: Mechanical Properties of Living Tissues, 2nd Edition, Springer - Verlag, 1993 (b) D. Boal, Mechanics of the Cell, 2001. (c) H. Lodish, D. Baltimore, L. Zipurksy, P. Matsudaira, Molecular Cell Biology, 2002. (d) K. Dill and S. Bromberg, Molecular Driving Forces, 2003 (e) J. Howard, Mechanics of Motor Proteins and the Cytoskeleton, 2001 (f) M. Mofrad and R. Kamm, Cytoskeletal Mechanics: Models and Measurements, 2006. (g) J. Humphrey, Introduction to Biomechanics, 2004. ...
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This note was uploaded on 11/11/2011 for the course BIO 2.797j taught by Professor Matthewlang during the Fall '06 term at MIT.

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