1.-Muscle architecture

1. Muscle contraction 1.-Muscle architecture 2.- Actin-myosin interactions and force generation 3.-Transverse tubules and calcium release 4.-Titin architecture and muscle elasticity Readings: 1.-Goldman YE. (1998) Wag the tail: structural dynamics of actomyosin. Cell. Apr 3;93(1):1-4. 2.-Huxley AF, Taylor RE. (1958) Local activation of striated muscle fibres. J Physiol. Dec 30;144(3):426-41. 3.-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. 2002 Aug 29;418(6901):998-1002.

2. Keywords: Sarcomere I band, A band, Z line Sliding filaments Myosin, actin, titin Tranverse tubular network Calcium release, Troponin complex Ryanodine and Dihydropyridine receptors

3. Problems: 1.-Muscle contraction triggered by an action potential has a latency of less than 10 ms for a 1 mm in thick, single frog muscle fiber. Is it plausible to claim that the calcium ions that trigger contraction enter mainly through the plasma membrane of the muscle fiber? In your answer consider that calcium ions move inside cells with a diffusion coefficient D in the range of 10-7 cm2/s. 2.-Describe the full sequence of events that start with a nerve impulse arriving at the neuromuscular junction, through muscle contraction and ending with relaxation of the muscle fiber. Write short one line descriptions of each event. 3.-The longest PEVK region of titin is about 2000 aa long. The contribution that a single aa makes to the contour length of the PEVK region is 0.36 nm. In thermal equilibrium calculate (roughly) the end-to-end length of this protein. Calculate its maximal extension and draw the force-extension relationship that you expect to observe.

13. Testing the sliding filaments hypothesis

29. Relaxed Contracting

31. “feet” Electron micrograph of a longitudinal section of a muscle fiber showing a full triad and also the connections (“feet”) between the T tubules and the sarcoplasmic reticulum. (180 000X )

36. Mechanisms of Ca2+ removal from the cytoplasm.

38. The elasticity of muscle is due to the Brownian motion driven collapse of a protein named titin Sprinter Brian Lewis

40. Muscle can contract and also can extend elastically

41. The elasticity of muscle results from the properties of a giant protein named Titin (from Titan!) Titin has a coiled region (PEVK) and a region folded into individual modules (I):

42. Machina Carnis

43. Is the elasticity of titin like that of a spring? The elasticity of a metal spring results from the stretching of the bonds between the metal atoms. Will titin also break if we pull it too far? Is this how titin works?

44. A metal wire in a spring extends by bond stretching and breaks by irreversibly disrupting its atomic arrangements Gold wire elastic extension (reversible) plastic extension (irreversible)

45. Electron micrographs of isolated titin molecules

46. We can stretch a single protein and measure how does the restoring force changes with the extension. mirrors laser Photodiode (Force) cantilever protein linear actuator (extension) .

49. detector can measure pico-Newton forces Actuator can extend a molecule by fractions of a nano-meter

50. How much is a pico (10-12) Newton of Force? Steam engine Protein unfolding mouse pico Newtons nano Newtons Newtons mega Newtons micro Newtons N kT Rice grain Average force exerted over 1 nm by thermal motion Force that ruptures a covalent bond Madonna