1. M. Basan A. Basu A. Callan-Jones J.F. Joanny F. Julicher K. Kruse T. Risler G.Salbreux K. Sekimoto R. Voituriez C. Sykes E. Paluch P. Pullarkat M. Bornens X. Sastres J.P. Henry E. Karatekim From cell to tissue dynamics?

4. Fibroblast Fragments Depolymerized Microtubules E. Paluch et al, E.480 Bornens et al, 1988

6. Filament array in lamellipodia (T. Svitkina and G.G. Borisy, 1999; Blanchoin et al.; Pantaloni et al., 2000, Ishiwata et al 2000) Arp 2/3

7. Actin Intrinsic Treadmilling ADP ATP Pi Actin-based motility

8. MYOSIN (R. Vale)

9. Muscles: Actin and Myosin Filaments titin

11. Conserved quantities, Broken symmetries Actin (monomer+polymer) Myosin (bound, unbound) Momentum (force) Polarization

12. Harvard Choice P.C. Martin et al

13. Conservation laws

14. Dissipative Reactive

15. A. Simha, S. Ramaswamy; T. Liverpool, C. Marchetti, H. Chaté

16. K. Takiguchi,1991 G. H. Koenderink 2006 F. Nedelec et al 1997, K. Kruse, F. Jülicher, 2000, T. Liverpool, C. Marchetti 2002, I. Aranson2005, B. Mulder et al 2005

18. Nematic Hydrodynamics ( F.M. Leslie, F. Brochard, P.G. de Gennes, P. Pieranski, E. Guyon ) x z

19. Spontaneous Frederiks transition H V R. Voituriez

20. Remains to be seen!

22. L. Giomi, C. Marchetti, J.F. Joanny, J.P.

23. Topological Singularities

24. Spontaneously moving topological singularity

25. State Diagram

26. EXPERIMENT (François Nedelec et al)

27. Allow for density variation:d=2

29. R. Goldstein B. subtilis S. Ramaswamy, G. Menon et al

30. Fluctuations?

31. Thermal noise

32. Non thermal fluctuations Long time limit Traveling wavesM. Sheetz, H.G. Dobereiner Always unstable at long wavelength!

33. z x y p Gel regime: non thermal noise important Fluid regime: nematic coupling important Particle (Vesicle), Diffusion

34. Short time: F. MacKintosh

35. L

36. “balistic” “diffusive” F. MacKintosh

37. New material Science Transitions toward moving sates “Ramaswamy waves” Unconventional diffusion Long wavelength unstable Similar to bacterial motion, flocks etc…

39. Questions Shape (profile) Relation thickness/force/velocity and flow Substrate, membrane tension What determines Length? A. Verkhovsky symmetry breaking?

40. Leading Edge Glycoprotéine Glycolipide Protéine Oligosaccharide Cholestérol Pore protéique Phospholipides

41. Leading edge and membrane dynamics

42. Steady motion

43. Threshold Leading edge

45. Thin slab U h x L/2 -L/2

46. U v=0v<0v>0 dd h Free ends Screening!

47. Lamellipodium shape and motion? h x v

48. x L d Keratocyte: In most cases d « L: Growth cone: A. Verkhovsky et al T. Betz + Stick-Slip! f cell

49. What determines Length?

50. Fragment

53. Fibroblast Fragments Depolymerized Microtubules E. Paluch et al, E.480 Bornens et al, 1988

54. Fibroblast Fragments Depolymerized Microtubules E. Paluch et al, E.480 Bornens et al, 1988

55. Actin Kinase Rho Kinase

56. P. Pullarkat, K. Jacobson

57. Cortical Actin? x z e Intrinsically unstable! T Spherical symmetry:Threshold!

60. Pramod Pullarkat

61. Frequency Activity Parameter Calcium sensitivity Activity parameter

62. Frequency

64. Mitosis? D. Bray, J. Spudich et al Stability of an active Shell Cell oscillations: M. Bornens et al, P. Pullarkat, K. Jacobsen

65. Tissue Dynamics

66. 4) Metastatic Inefficiency Cameron et al., Cancer Research (2000)

67. Measurement of Active Tissue Homeostatic Pressure Numbers?

68. Stationary State:

69. Tissue Fight for Space

70. 3) Tumor Growth Dynamics a) Compartment Competition Force balance: (Liquid limit: ) Constitutive eqns : Highest Stationary pressure wins again!

71. 4) Metastatic Inefficiency Surface tension for at tumor boundary:  Tumor grows  Tumor shrinks Critical Radius! If  const If   faster than r « Benign » steady state

72. Small tumors are monoclonal How do you reach the critical radius?

73. Nutrition/Signalization: millimeter size Steady State Stability versus Angiogenesis? Duplicating cells Migrating cells Necrosed cells

74. Find? r c a few cell diameter Very sensitive on  Preferential nucleation at rigid interfaces Seed and soil (Stephen Paget 1889) Papillomas virus But many other steps…

75. Messages : Quantitative cell dynamics Signalization, Fluctuations Axones, synapses and Alzheimer Tissue dynamics: new concepts, new experiments Much to do!