PHYS 469G/569G - Fall 2002
Cell and Molecular Biophysics

Call number: 06539 (469G) or 06540 (569G)
Credit hours: 3
Classroom: 332 Clippinger Labs
Day and time: MW 2:10 - 4:00 p.m.
Prerequisite: Physics 253
Instructor: David F. J. Tees, Assistant Professor
Ohio University


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Announcements

As of Fall quarter 2004, this experimental course has been replaced by the permanent course numbered PHYS 461/561. I will keep this page up for archival purposes, but any links should be adjusted to the newer course.

11/11/02 1:30 p.m.: Assignment #4 is now available for download. PDF (19k)

11/11/02: The solutions to Assignment #3 are now available for download. PDF (39k)

10/15/02 6:50 p.m.: Assignment #3 is now available for download. PDF (21k)

10/14/02: The solutions to Assignment #2 are now available for download. PDF (31k)

10/14/02 Reading for the Wednesday Oct 16 class: George I. Bell, Models for the specific adhesion of cells to cells, Science, 200:618-627, 1978. This paper is rather long, but it is a classic and full of useful biophysical insights. A pdf file available.

10/1/02 Reading for Wednesday's class: Harold P. Erickson, Stretching single protein molecules: titin is a weird spring, Science, 276:1090-1092, 1997. This is an HTML version of the text of the paper and the very nice figure. There doesn't seem to be a pdf file available.

9/29/02 8:30 p.m.: Assignment #2 is now available for download. PDF (16k)

9/29/02 8:30 p.m.: The solutions to Assignment #1 are now available for download. PDF (35k)

9/12/02 8:30 p.m.: Assignment #1 is now available for download. MS Word (36k) | Rich Text Format (52k) | PDF (15k)


Course Description: A course introducing the physical principles that underlie phenomena in cell biology as well as properties of biological macromolecules as "soft" materials. Topics covered will include an introduction to cell and molecular biology for students in the physical sciences, biorheology, Brownian motion and diffusion, molecular interactions in macromolecules, polymer physics of DNA, RNA and proteins, protein and nucleic acid structure, chemical kinetics, mechanical and adhesive properties of biological molecules, AFM, NMR, SPR, fluorescence, optical tweezers, and other micromanipulation techniques, cell membrane structure and mechanical properties, membrane channels and pumps, and molecular motors.

For more information, contact Dr. Tees at tees@ohio.edu or 593-1694.


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. In the 19th century, biophysical insights from animal metabolism, blood flow and neuroelectricity were the inspiration for developments in thermodynamics, electrodynamics, and fluid mechanics. Since then, 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. Biopolymers form a new class of “soft” materials that are reproducibly assembled from a small range of building blocks to form single molecules that are, nevertheless, large collections of atoms. These systems are often far from equilibrium and exhibit complex emergent phenomena that are non-trivial consequences of the underlying physical laws. In this way, physics has much to learn from biology. For example, biomimesis—mimicking the way biology has contrived to solve the problem of allowing complexity be self-assembled—promises insight into the construction of nanomachines. This course will provide a grounding in the physical principles underlying molecular and cellular biology.


Textbooks and other resources

No single up-to-date text covers all topics in this course. Notes from the instructor will form the primary course material. Readings from the literature will be assigned. The following resources may prove useful, although none are required:

Biophysics Textbook Online: (free) Students can download sections freely from this resource prepared by the Biophysical Society. The site features articles written by experts in individual areas and is relatively up-to-date. It is, however, a work in progress and not all topics are covered.

Alberts et al., Molecular Biology of the Cell: ($102) This introductory cell and molecular biology textbook is a standard reference, good for both the undergraduate and graduate level. The introduction to molecular biology will be based on this book. A copy has been placed on reserve at Alden Library.

Howard C. Berg, Random Walks in Biology ($20) is an excellent reference for diffusion and Brownian motion. This book is available on Amazon.com and makes a useful addition to any library. A copy has been placed on reserve at Alden Library

Michel Daune, Molecular Biophysics ($60) is a popular modern textbook which covers some of the material in the course. The material in this translation is rather dense, though. A copy has been placed on reserve at Alden Library.

Jacob Israelachvili, Intermolecular and Surface Forces, ($78) is still the standard reference for intermolecular forces. A copy has been placed on reserve at Alden Library

Paul C. Hiemenz and Raj Rajagopalan Principles of Colloid and Surface Chemistry ($70) 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).

C. R. Cantor & P. R. Schimmel, Biophysical Chemistry pts I, II & III, (1980) 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) and probably the most useful for this course. 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).

D. L. Lauffenburger and J. L. Linderman Receptors: models for binding, trafficking, and signaling ($50) is a good reference for receptor-ligand binding, signaling, cell adhesion and migration. Copies are available on Amazon.com.


Web resources

Biophysics Textbook Online This page is an attempt to produce an updated biophysics textbook that can be downloaded and used cheaply by students. The coverage is wide, but the textbook is still somewhat incomplete and the level of the text is rather variable.
Harold P. Erickson, Stretching single protein molecules: titin is a weird spring, Science, 276:1090-1092, 1997. 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.
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).
Brookhaven 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.
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".
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. Sadly, at the moment papers less than six months old cannot be accessed from Ohio U. I'm hoping that this will change during the course of the semester (I have requested that the library get a proper subscription). If you want to get the full copy of an article (based on reading the abstracts, which are accessible) let me know, and I'll get you a PDF.
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!
Physical Review Letters Top North American physics journal. This journal sometimes has biophysics articles in final "Muldisciplinary physics" section at the end of each issue.


Course Outline (tentative)

Date Topic
Sept. 9 Cell structure: membrane, nucleus, organelles. Access pdf file of overheads
Sept 11 Biological macromolecules: proteins, DNA, carbohydrates Access pdf file of overheads
Sept 16 Thermodynamics of bonds and statistical mechanics Access pdf file of overheads
Sept 18 Covalent and non-covalent interactions Access pdf file of overheads
Sept 23 last day to add or drop a course with no grade Colloidal interactions and DLVO theory Access pdf file of overheads
Sept 25 Brownian motion and diffusion Access pdf file of overheads
Sept 30 DNA, RNA and protein structure, NMR, X-ray crystallography Access pdf file of overheads
Oct 2 Polymer chain structure; Techniques for applying force to molecules Access pdf file of overheads
Oct 7 Techniques for applying force to molecules, Law of Mass Action, Helix-coil transition Access pdf file of overheads
Oct 9 DNA mechanics; midterm exam
Oct 14 last day to withdraw Reaction rates, Scatchard analysis, SPR Access pdf file of overheads
Oct 16 Cell adhesion, force dependence of rates, rolling Access pdf file of overheads
Oct 21 force dependence of rates, rolling, forced unbinding Access pdf file of overheads
Oct 24 Cytoskeleton; Molecular motors, Brownian ratchets Access pdf file of overheads
Oct 28 Cell membrane mechanics; micropipette aspiration Access pdf file of overheads
Oct 30 Signaling; channels and pumps; patch clamping Access pdf file of overheads
Nov 4 Extracellular matrix mechanics Access pdf file of overheads
Nov 6 Migration, Blood rheology Access pdf file of overheads
Nov 11 Veterans’ Day No class
Nov 13 Blood rheology, blood clotting, student presentations Access pdf file of overheads
Nov 18 Last day of class Review, student presentations
Nov 21 2:30 p.m. Final Exam (to be held in class)s


Assignments

There will be four assignments consisting of problems and activities that will reinforce and give practical experience concerning topics covered in class. Completed assignments will be due on the following schedule:

Assignment 1: 2:00 p.m. Monday, Sept 23

Assignment 2: 2:00 p.m. Wednesday, Oct 9

Assignment 3: 2:00 p.m. Monday, Oct 28

Assignment 4: 2:00 p.m. Monday, Nov 25

Assignments may be placed in my mailbox in 251A Clippinger or slid under the door of my office (357A Clippinger).


Presentation (Graduate Students Only)

Graduate students will be required to present a recent paper from Biophysical Journal, or a similar journal 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 will be scheduled in consultation with the students.


Quizzes

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)


Marking Scheme

Undergraduate Graduate
Participation 5 5
Assignments (5) 40 20
Quizzes (10) 5 5
Midterm exam 25 25
Final exam 25 25
Presentation - 20


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