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LON-CAPA

Text Books

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Tentative Schedule

Grading Scheme

PHYS 461/561 - Fall 2008
Cell and Molecular Biophysics

Call number: 05634 (PHYS 461) or 05648 (PHYS 561)
Credit hours: 4
Classroom: 132A Clippinger Labs
Day and time: MTWF 12:10-1:00 p.m.
Prerequisite: (Undergrad: PHYS 253, CHEM 152, BIOS 170) (Graduate: Permission of instructor)


Course Description:

Introduction to the physical principles that underlie phenomena in cell biology and the properties of biomolecules. Topics covered will include an introduction to cell and molecular biology, biorheology, Brownian motion, molecular interactions in macromolecules, protein and nucleic acid structure, physics of biopolymers, chemical kinetics, mechanical and adhesive properties of biomolecules, molecular manipulation techniques, cell membrane structure, membrane channels and pumps, molecular motors.


Instructor: David F. J. Tees, Associate Professor, Ohio University

Office: 357A Clippinger Labs
Phone: 593-1694
E-mail: tees@ohio.edu


Announcements

Graduate students should come and see me to register. When you come to see me, we will talk briefly about the biology knowledge required and then I will pink slip you into the class.

The lecture notes and assignment solutions will be made available on the LON-CAPA system. Click on this link to go to loncapa.phy.ohiou.edu to go to the logon page. You will need to log in with your oak ID and then click on the Cell and Molecular Biophysics role. There are links to the material on the introductory page.


Purpose

As the scientific world becomes more multidisciplinary, it will become increasingly necessary for physical scientists and engineers to be aware of the challenges and opportunities in cellular and molecular biology. Biological scientists can also benefit from a grounding in the mathematical background commonly given to physicists. Biophysics uses theoretical and experimental techniques from physics to model biological phenomena and to understand how organisms can consistently assemble complex molecules and cellular interactions from simple organic chemicals. Techniques such as X-ray crystallography, nuclear magnetic resonance, electron microscopy and electrophoresis have contributed enormously to the toolkit of molecular biologists. Scanned probe microscopies, optical trapping, and new spectroscopic techniques promise a further revolution in molecular precision. Concepts from polymer and colloid science and statistical and thermal physics are an important basis for understanding cell and molecular biology. This course will provide a grounding in the physical principles underlying molecular and cellular biology.


Textbooks and other resources

Notes from the instructor will form the primary course material. Readings from the literature will be assigned. Graduate students who have not taken BIOS 170 are required to get a copy of the following introductory textbook (a used, older edition copy will be fine)

Alberts et al., Molecular Biology of the Cell ($99 new, 5th edition, but I recommend getting a used 4th or 3rd edition. The biophysics parts are essentially unchanged in the 4th edition and a used copy can be got for as low as $7 - $15). The introduction to molecular biology will be based on this book. This book is regularly referenced for general things in the biophysics literature and having a copy for reference will be very useful for your future.

The following text is recommended for graduate students (but not required). Copies will be placed on reserve at Alden Library:

Philip Nelson’s Biological Physics: Energy, Information and Life, W.H. Freeman and Co., New York, 2004 ($83 on Amazon.com as of Sept 2, 2008. Used copies are also available on Amazon,com for a bitless).

Other useful resources:

Copies of all of the following books (plus the texts above) will be placed on reserve at Alden Library.

Howard C. Berg, Random Walks in Biology ($25). This is an excellent introduction to diffusion and Brownian motion.

D. Boal, Mechanics of the Cell ($55). This is an excellent reference for cell mechanical properties.

C. R. Calladine & H. R. Drew, Understanding DNA ($60). This is a wonderful reference for the structure of DNA.

Paul C. Hiemenz and Raj Rajagopalan, Principles of Colloid and Surface Chemistry ($70). This is an excellent reference for colloidal phenomena, diffusion and Brownian motion. A copy can be accessed online through the library website (see me for advice if you have trouble finding it or installing the DJvu reader).

Jacob Israelachvili, Intermolecular and Surface Forces ($78). This is still the standard reference for intermolecular forces.

D. L. Lauffenburger and J. L. Linderman Receptors: models for binding, trafficking, and signaling ($85). This is a good reference for receptor-ligand binding, signaling, cell adhesion and migration.

C. R. Cantor & P. R. Schimmel, Biophysical Chemistry pts I, II & III (1980). This is the classic text for molecular biophysics. These volumes are still in print and quite relevant, but they are expensive (a full set costs $250 new). Part III is the least expensive ($70) but the most useful. It could serve as a reference for the middle part of the course as it covers the behavior of biological macromolecules (with good sections on polymer dynamics and receptor-ligand binding).


Web resources

Harold P. Erickson, Stretching single protein molecules: titin is a weird spring, Science, 276:1090-1092, 1997. This article discusses entropic springs which are ubiquitous in biology.
Edward M. Purcell, Life at Low Reynolds Number, Am. J. Phys., 45:311, 1978. This is a wonderful, though chatty, article on how bacteria and cells experience very different everyday physics from what people experience. An html version (with figures) can be downloaded from the web, or see me for a copy.
Movies of Bacteria moving This is Howard Berg's site at the Rowlands Institute at Harvard U. It has movies of bacteria executing their persistent random walk (it requires Quicktime and it may be a bit quirky).
Protein Data Bank This database stores and dispenses information on the DNA and amino acid sequences and X-ray and NMR structures of proteins. One can download RASMOL (the viewer for protein structures) here. There's a very useful index to the PDB that breaks down the proteins by class
PDB at a Glance This nice site has an index of protein structures from the Protein Data Bank that have been sorted by function. This is a good way to browse the database. It allows one to find the four character codes for interesting proteins without having to know exactly what one is looking for in advance. The site's viewer doesn't work very well for me, so you'll probably want to just get the code and go to the protein databank and download the protein there.
National Center for Biotechnology Information This is the National Institutes of Health's clearinghouse for all of the national and international DNA and protein sequence and structure databases. One can get to GENBANK (the storehouse for DNA sequences by using clicking on the "Entrez" button and clicking on "Entrez--nucleotide". Another useful resource for the Genome is at the Nature website on the genome: Nature Genomics
Reading Frames in DNA This site has a nice tutorial on various aspects of DNA sequence analysis
Biophysical Journal The journal of the Biophysical Society and the best one to check out for papers of interest.
Proceedings of the National Academy of Sciences U.S.A. The journal of The National Academy of Sciences of the U.S.A. This is a high prestige journal. There are usually 3-6 biophysics papers per issue (in a separate section) and these are often excellent papers!


Tentative Course Outline (subject to change)

Date Topic
Sept. 8 Intro to Biophysics, size hierarchy, microscopy
Sept. 9 Intro to cell biology: diversity of cellular life, cell structure
Sept. 11 Intro to molecular biology: Small molecules, carbohydrates, DNA, RNA
Sept. 12 Proteins; Microscopy lab (Clippinger 352)
Sept. 15 Probability distributions; Gaussians (Assignment 1 due)
Sept. 16 Laws of thermodynamics & kinetic theory
Sept. 18 Statistical mechanics and Boltzmann factors
Sept. 19 Diffusion and Brownian motion
Sept. 22 Fluids, viscosity and Avogadro's number
Sept. 23 Life at Low Reynolds Number
Sept. 25 Bonds and Free energy
Sept. 26 Electrostatic and van der Waals interactions
Sept. 29 Hydrophobic interactions; Protein structure (Assignment 2 due)
Sept. 30 Protein characterization; Colloidal interactions
Oct. 2 Guest lecture (Dr. Tees at BMES meeting)
Oct. 3 Midterm exam
Oct. 6 Colloidal interactions; adhesion
Oct. 7 Cell adhesion I: introduction to immunology
Oct. 9 Reaction rates and equilibrium constants (Assignment 3 due)
Oct. 10 Cell adhesion II: single molecule forced unbinding
Oct. 13 Cell adhesion III (last day to drop class)
Oct. 14 Cell adhesion IV
Oct. 16 DNA structure, twisting and wrinthing
Oct. 17 Dynamics of DNA and RNA I
Oct. 20 Forced unfolding and mechanics of DNA and RNA II
Oct. 21 Mechanics of proteins (Assignment 4 due)
Oct. 23 Cytoskeleton; Molecular motors
Oct. 24 Molecular motors under load
Oct. 27 Molecular motors and enzyme kinetics I
Oct. 28 Brownian ratchets and enzyme kinetics II
Oct. 30 Membrane channels and pumps; patch clamping
Oct. 31 Nernst potential and Donnan equilibrium I
Nov. 3 Cell membrane mechanics; micropipette aspiration I
Nov. 4 Cell membrane mechanics; micropipette aspiration II
Nov. 6 Cell membrane mechanics; micropipette aspiration II
Nov. 7 Mechanical properties of cytoskeleton and extracellular matrix (Assignment 5 due)
Nov. 10 Extracellular matrix and cell migration
Nov. 11 Veterans' Day observed (No Classes)
Nov. 13 Blood rheology: Poiseuille flow and Murray's Law
Nov. 14 Biomedical Ethics (Assignment 6 due; Last day of classes)
Nov. 19 Wednesday, 12:20 p.m. Final Exam (to be held in class)


Assignments

There will be at about 7 short assignments (a bit fewer than 1 per week) consisting of problems and activities that will reinforce and give practical experience concerning topics covered in class. There will be separate assignments for graduate and undergraduate student. Completed assignments will be due as listed on the tentative schedule. Assignments may be given to me in class, placed in my mailbox in 251A Clippinger Labs or slid under the door of my office (357A Clippinger). They must be in by 5:00 p.m. on the due date.


Presentation (Graduate Students Only)

Graduate students will be required to present a recent paper from Biophysical Journal or the biophysics section of Proceedings of the National Academy of Sciences U.S.A. on a topic of their own choosing or suggested by the instructor. The presentations will take place in the later half of the course and may be done as part of the Biophysics Journal club.


Quizzes

Eight to Ten short quizzes on biological nomenclature will be given at the ends of some classes to ensure that students learn the biological language they will need to communicate productively with colleagues.


Exams

There will be midterm exam and a final exam (see the schedule above)


Grading Scheme

Undergraduate Graduate
Midterm exam 25 25
Final exam 25 25
Quizzes (8-10) 7 7
Assignments (~7) 40 20
Presentation - 20
Participation 3 3


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