1. Lecture 3/4 Rob Phillips California Institute of Technology (Block et al.) (Wuite et al.)

2. Reduced Description of Protein Structure

3. Single Molecule Experiments: A Reminder There are a variety of techniques for measuring the relation between force and extension for single molecules. This domain has been dubbed dynamical force spectroscopy.

4. DNA as a Case Study in Single Molecule Biomechanics Force-extension curves for DNA have served as a testbed for the quantitative analysis of the deformation of macromolecules. (Lieber et al.)

5. Atomic Force Microscopy as a Single Molecule Probe Atomic force microscopy provides a complementary way of measuring the action of the molecules of life when subjected to force. Single molecule analog of the Instron machine. Dynamical Force Spectroscopy – each molecule has its own force/extension signature. (Fernandez et al.)

6. Single Molecule Experiments with the AFM (Fernandez et al.) Concrete example of dynamical force spectroscopy in the case of the giant muscle protein titin. Key modeling challenge: the precise details of the force/extension curve. Note that by performing mutations on the titin molecule, the force/extension signature can be altered.

7. Muscle structure

9. Viral Packing: Relevant Scales Equilibrium entropic size of unpacked DNA: Capsid size = 40nm (Hendrix) Persistence length of DNA, length over which DNA can be thought of as being stiff. There is a negative charge every.17nm of length along DNA – electrostatic energy crucial also.

10. E. Coli from Lehninger

11. DNA Force Extension