1. Time table Hugh Huxley Introduction. 6 mins. X-ray interference experiments 28 mins. on whole muscles. Yale Goldman Structural dynamics of individual 28 mins. myosin molecules in real time. Ken Holmes The structural basis of the crossbridge 28 mins. cycle. Linear Motors

2. LINEAR MOTORS Linear motors are molecular machines which can transform chemically stored energy in ATP into directed force and linear movement. How do myosin heads produce force and linear movement in actin based systems?

3. Relative sliding of arrays of actin and myosin filaments produced by cross-bridges causes muscle contraction

4. Myosin V Stalk Cargo Binding Domain Calmodulins Motor Domains Actin Filament 37 nanometers

8. Myosin V Stalk Cargo Binding Domain Calmodulins Motor Domains Actin Filament 37 nanometers

9. The Key Problems: we need to a) Show that the structure of the myosin molecule could plausibly undergo the large shape change required. b) Show that such a cyclical structural change actually takes place in a contracting muscle.

10. X-ray crystallographic structure of myosin sub-fragment one [S1].

15. X-ray interference experiments on whole muscles. Hugh Huxley. Rosenstiel Center, Brandeis Univ., Waltham, Mass. U.S.A. huxley@brandeis.edu

20. The experiments do provide good evidence that the lever arms tilt during the working stroke, and that they and the catalytic domains move inwards towards the centre of the A-band by the amounts expected on the tilting lever arm model

21. Somewhat unexpectedly, the attached heads in isometric contraction are concentrated around the beginning of the working stroke, rather than being spread out fairly uniformly as envisaged in some models. Presumably, ones that were attached further into the stroke have detached and not been replaced as the contraction became isometric. So, what happens during steady shortening?

23. A.F.Huxley-Simmons quick release experiment, showing very rapid initial tension recovery.