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