Force-spectroscopy of single proteins

1. Force-spectroscopy of single proteins II: mechanical engineering in biological systems

2. Igor Demonstration of analysis with models of polymer elasticity

3. Reverse Engineering of the giant muscle protein titin

5. The elastic protein titin is the third filament of muscle

6. Electron micrographs of isolated titin molecules

9. Machina Carnis

10. Titin: a complex mechanical protein A B C D Adapted from Linke, 2007, Cardiovascular Research (in press)

11. Measuring the extensibility of titin in a single isolated cardiac fiber

17. Elasticity of PEVK

18. Electron micrographs of PEVK_I27 polyprotein

19. Persistence length of PEVK

20. Elasticity of N2B

26. V11P V15P V13P wt Y9P

27. Understand the mechanical design of titin in humans Understand the molecular design of its modules Create titin phenotypes in mice

28. Mechanical design of the extracellular matrix:fibronectin

29. A complex web of proteins and polysaccharides that provides the mechanical scaffold for organs and tissues ECM cell membrane

30. Fibronectin: a major, cell binding component of the ECM NMR structure of 10F3. The RGD residues are identified in the picture.

32. Fluorescently labeled fibronectin assembled by CHO cells

38. Mechanical unfolding of protein domains helps to keep the cells mechanically bonded. Mechanical hierarchies define the triggers of cellular activity Cell binding cryptic binding cryptic binding

39. Mechanical design of the extracellular matrix:polysaccharides

40. Polysaccharides cellulose amylose

41. 0.55 nm 0.45 nm If we mechanically stretch a sugar ring, it gets longer by switching from a chair to a boat conformation

43. Periodate oxidation cleaves the rings of pectin

46. Ubiquitin chains form a mechanical signallingsystem in cells

48. From Weissman, Nature Reviews, 2001, 2:169-178