Readings in Biophysics: from Single Molecules to Networks

Biology W4070

Fall 2004



Julio Fernandez |

Mike Sheetz |

Rafa Yuste |


Wednesday 4:10-6:00pm

800 Fairchild



This will be an interdisciplinary course that will bridge the interests of students from several different departments such as: Biology, Chemistry, and Physics. This will focus on a quantitative understanding of biological systems, from single molecules to different types of biological networks.



calculus, chemistry, physics, 1 year biology, or instructors' permission


Course Description:

Plan for course: In each class meeting, one or more classic papers will be discussed, including background. Each student will present a figure from the paper or come prepared with at least one question about the paper. An Example of the papers to be discussed is given below(subject to change).  You will be able to download these papers from the Columbia library web site. Grading will be based on participation in discussion and a final that will consist of writing a three-page critique of a relevant paper. 


Reading List:

The course will make use of original scientific material published in the journals: Nature, Science, PNAS, and other journals. The class will meet once per week to discuss 1-3 assigned original research articles.


Course Requirements:

Oral presentations of scientific papers


Reading List for Proferssor Fernandez:


Itoh H, Takahashi A, Adachi K, Noji H, Yasuda R, Yoshida M, Kinosita K. (2004).

Mechanically driven ATP synthesis by F1-ATPase.
Nature. 427(6973):465-8.



Li H, Linke WA, Oberhauser AF, Carrion-Vazquez M, Kerkvliet JG, Lu H, Marszalek PE, Fernandez JM. (2002).

Reverse engineering of the giant muscle protein titin.
Nature. 418(6901):998-1002.


Liphardt J, Onoa B, Smith SB, Tinoco I JR, Bustamante C.

Reversible unfolding of single RNA molecules by mechanical force.
Science. 2001 Apr 27;292(5517):733-7.


Strick TR, Croquette V, Bensimon D. (2000).

Single-molecule analysis of DNA uncoiling by a type II topoisomerase.
Nature. 404(6780):901-4.


Berg, H.C.

Random Walks in Biology.

Princeton: Princeton University Press. Revised 1993.

(read 2 or 3 selected chapters)



Reading List for Proferssor Sheetz:


Marshall BT, Long M, Piper JW, Yago T, McEver RP, Zhu C. (2003).
Direct observation of catch bonds involving cell-adhesion molecules.
Nature. 423(6936):190-3.



Nishiyama M, Higuchi H, Yanagida T. (2002).
Chemomechanical coupling of the forward and backward steps of single kinesin molecules.
Nat Cell Biol. 4(10):790-7.



Yildiz A, Forkey JN, McKinney SA, Ha T, Goldman YE, Selvin PR. (2003).
Myosin V walks hand-over-hand: single fluorophore imaging with 1.5-nm localization.
Science. 300(5628):2061-5.



Maier B, Potter L, So M, Long CD, Seifert HS, Sheetz MP. (2002).
Single pilus motor forces exceed 100 pN.
PNAS. 99(25):16012-7.


Erratum in: PNAS. 2003 May 13;100(10):6287.



Reading List for Proferssor Yuste:


Bray D, Levin MD, Morton-Firth CJ. (1998).

Receptor clustering as a cellular mechanism to control sensitivity.
Nature. 393(6680):85-8.



Jaeger H, Haas H. (2004).
Harnessing nonlinearity: predicting chaotic systems and saving energy in wireless communication.
Science. 304(5667):78-80.



Alon U, Surette MG, Barkai N, Leibler S. (1999).
Robustness in bacterial chemotaxis.
Nature. 397(6715):168-71



Watts DJ, Strogatz SH. (1998).
Collective dynamics of 'small-world' networks.
Nature. 393(6684):440-2.

Other Readings in Biophysics:


Rotation of F1-ATPase. Yasuda, R., H. Noji, M. Yoshida, K. Kinosita, Jr., and H. Itoh. 2001. Resolution of distinct rotational substeps by submillisecond kinetic analysis of F1-ATPase. Nature. 410:898-904.


Myosin V Motility. Yildiz, A., J.N. Forkey, S.A. McKinney, T. Ha, Y.E. Goldman, and P.R. Selvin. 2003. Myosin V walks hand-over-hand: single fluorophore imaging with 1.5-nm localization. Science. 300:2061-5.


Reversible Unfolding of Single RNA Molecules by Mechanical Force.

Liphardt, J., B. Onoa, S. Smith, I. Tinoco, and C. Bustamante. Science. 292:733-737.


Milo R, Itzkovitz S, Kashtan N, Levitt R, Shen-Orr S, Ayzenshtat I, Sheffer

M, Alon U. Superfamilies of evolved and designed networks.

Science. 2004 Mar 5;303(5663):1538-42.


Taga ME, Bassler BL.   

Chemical communication among bacteria.

Proc Natl Acad Sci U S A. 2003 Nov 25;100 Suppl 2:14549-54. Epub 2003 Aug 29.


Guet CC, Elowitz MB, Hsing W, Leibler S. 

Combinatorial synthesis of genetic networks.

Science. 2002 May 24;296(5572):1466-70.


Hopfield, J. J. (1995). Pattern recognition computation using action potential timing for stimulus representation. Nature 376:33-36.


Wehr, M., Laurent, G. " Odour encoding by temporal sequences of firing in oscillating neural assemblies" Nature 1996 Nov 14; 384(6605):162-6.


Wang, XJ. "Synaptic reverberation underlying mnemonic persistent activity" Trends Neurosci 2001 Aug; 24(8):455-63.


Dobrunz, L. E., and C. F. Stevens. (1999). "Response of hippocampal synapses to natural stimulation patterns" Neuron 22:157-66.


Single molecule fluorescence measurements (Diffusion in Nucleus) Kues, T., A. Dickmanns, R. Luhrmann, R. Peters, and U. Kubitscheck. 2001. High intranuclear mobility and dynamic clustering of the splicing factor U1 snRNP observed by single particle tracking. Proc Natl Acad Sci U S A. 98:12021-6.


Tying a molecular knot with optical tweezers. Arai, Y., R. Yasuda, K. Akashi, Y. Harada, H. Miyata, K. Kinosita, Jr., and H. Itoh. 1999. Tying a molecular knot with optical tweezers. Nature. 399:446-8.


Molecular Dynamics of Channels. Grayson, P., E. Tajkhorshid, and K. Schulten. 2003. Mechanisms of selectivity in channels and enzymes studied with interactive molecular dynamics. Biophys J. 85:36-48.


Effects of Force on Single Bond Lifetimes. Evans, E. 2001. Probing the relation between force--lifetime--and chemistry in single molecular bonds. Annu Rev Biophys Biomol Struct. 30:105-28.


Force Increases the Lifetime of Catch Bonds. Marshall, B.T., M. Long, J.W. Piper, T. Yago, R.P. McEver, and C. Zhu. 2003. Direct observation of catch bonds involving cell-adhesion molecules. Nature. 423:190-3.


RNA Packaging into a Phage Capsid. Smith, D.E., S.J. Tans, S.B. Smith, S. Grimes, D.L. Anderson, and C. Bustamante. 2001. The bacteriophage straight phi29 portal motor can package DNA against a large internal force. Nature. 413:748-52.


Topoisomerase Action on Supercoiled DNA. Charvin, G., D. Bensimon, and V. Croquette. 2003. Single-molecule study of DNA unlinking by eukaryotic and prokaryotic type-II topoisomerases. Proc Natl Acad Sci U S A. 100:9820-5.


Probing protein - protein interactions in real time. Viani, M., L. Pietrasanta, J. Thompson, A. Chand, I. Gebeshuber, J. Kindt, M. Richter, H. Hansma, and P. Hansma. Nature Structural Biology. Vol. 7. No. 8: 644-647.


Chemomechanical coupling of the forward and backward steps of single kinesin molecules

Nishiyama, M., H. Higuchi, and T. Yanagida. Nature Cell Biology. Vol 4: 790-797.


Distinguished Inchworm and Hand-Over-Hand Processive Kinesin Movement by Neck Rotation Measurement

Hua, W., J. Chung, and J. Gelles Science. 295: 844-848.