1. Cellular and Tissue Mechanics Jim PierceBi 145a Lecture 4, 2009-2010

2. Cellular Mechanics Cell Physiology is really the study of cellular mechanics.

3. Cellular Mechanics Cells act both as solids and fluids. Structural functions require solid cells. Many cell functions require fluidity. A dynamic cytoskeleton allows the cell to achieve this goal.

4. Cellular Mechanics A cell has material properties Described using materials science APh/BE 161 – Physics of Biological Structure A cell has fluid properties: Described using fluid mechanics Be/Ae 243 – Biofluid Mechanics A cell has membrane properties Lots of ways to describe! Bi 211 – Topics in Membrane and Synapse Physiology

5. Cellular Mechanics Rather than try to supplant these courses, we will introduce some of the terminology If you’re really interested in Bioengineering, I encourage you to take those classes!

6. Mechanics What is a material? … A tangible substance that makes a physical object. What can we do to a material? Expose it to force … a.k.a. Load

7. Mechanics Types of Loads:

8. Mechanics Combined Loads Bending Twisting

9. Material Properties How does the material respond to Load? Strength Resilience Toughness Elastic Plastic Failure

10. Stress Strain Curve Strain = elongation / equilibrium length Stress = applied force / cross-sectional area

11. Stress Strain Curve Elastic – When a Load (Strain) results in a linear stress profile (example = spring)

12. Stress Strain Curve Yield Point – The Load that cannot be elastically absorbed.(i.e. the material absorbs load)

13. Stress Strain Curve Failure – When the load ultimately breaks the material(hence ultimate strain)

14. Failure

15. Stress Strain Curve Plastic – when a load deforms a material and changes the structure of the material

16. Stress Strain Curve Similar to Pressure-Volume Curve Area = Work Volume Pressure Volume

17. Stress Strain Curve Resilience = area of elastic region Toughness = area of elastic and plastic regions

18. Stress Strain Curve “Shock Absorber” Starting Point

19. Stress Strain Curve “Resilient Connector” Starting Point

20. Cellular Mechanics One advantage that cells, tissues, and organs have over other materials… They are constantly remodeled. That means: Failures can be repaired Cells can change the properties of the Tissue

21. Cellular Mechanics Loads, as forces, are the same for fluids The difference between a fluid and solid Is in the response to shear stress Solids respond with recoverable deformation Fluid respond with irrecoverable flow

22. Fluid Mechanics How do we describe a fluid and its environment? Pressure and Volume Velocity and Flow Density Viscosity Types of Flow Compressibility

23. Fluid Mechanics Viscosity – how much you put into it versus how much you get out of it

24. Fluid Mechanics Viscosity = slope of stress / strain

25. Fluid Mechanics Viscosity

26. Fluid Mechanics Types of Flow Although there are many different patterns that can be seen when examining fluid flow… There are really only two types:

27. Fluid Mechanics Turbulent Flow

28. Fluid Mechanics Laminar Flow

29. Cellular Mechanics A cell has membrane properties Surface Tension Membrane Conductance Membrane Capacitance Adhesion Tendancy Membranes are well discussed in Bi/CNS 150

30. Cellular Mechanics Loading the Cell Consider the Erythrocyte Stress (Scalar) Strain Forces Compression / Expansion Shear Forces Membrane Tension and Elasticity

31. Cellular Mechanics Red Cell Membrane

32. Cellular Mechanics Responses To Stress Lengthening/shortening Forces Compression / Expansion Resist the force (cytoskeleton) Accept the force (change cell volume) Shear Forces Membrane Tension Resist the force (cytoskeleton, membrane fluidity) Accept the force (bending, elasticity)

33. Cellular Mechanics Why does Sickle Cell Disease cause Anemia? Hypoxemia and Stress cause sickling of the mutant hemoglobin. Sickled hemoglobin deforms the cell. The cell responds to deformation by membrane fluidity changes (less viscous) The reticuloendothelial system destroys these abhorrent cells. (hemolytic anemia)

34. Cellular Mechanics Thus, Sickle Cell Anemia is a Hemolytic Anemia! (so are most hemolytic anemias)

35. Cellular Mechanics How does the cell know it is being deformed? There are membrane proteins that transduce signals based on surface tension. The cytoskeleton and associated proteins transduces signals based on strain. The cytosol viscosity exerts flux control and concentration control on metabolic pathways.

36. Cellular Mechanics Cell Strain Energy All cells have potential energy stored in the structure of the cytoskeleton. The sensory neurons in muscles and tendons tranduce strain energy all the way to an action potential. Most other cells just use strain energy to adjust the cytoskeleton structure.

37. Cellular Mechanics Cell Adhesion also occurs in the blood Under most circumstances, all blood cells try to keep from sticking to the wall. When a Leukocyte goes on the hunt… Cell Rolling Cell Adhesion

38. Cellular Mechanics Movie by Steven House, PhD During his fellowship at Columbia

39. Cellular Mechanics The blood cell is an excellent example of cellular mechanics. But we can expand these concepts to other cell types and tissues, too!

40. Cell Examples Primary sensory neurons in the dermis Merkel cell of epidermis (touch sensor) Serosal Cell of the body cavities Transitional Epithelium

41. Skin and the Nervous System

42. Merkel Cell Unknown origin (Likely Neural Crest) Embedded in Epidermis Light Touch

43. Pacini Corpusle

44. Neural Crest origin Bipolar Sensory Neuron Located in Dermis Deep touch Pacini Corpusle

45. Hair Sensation Free neuron Attached to base of hair Hair movement

46. Serosa

47. Derived from intraembryonic coelome Lines the body cavities

48. Transitional Epithelium Lines the bladder RelaxedContracted

49. Tissue Mechanics Shear Stress on the Blood Vessels Changes the morphology of endothelial cells Increases production of stress-response elements, cellular adhesion molecules, cytokines, and nitric oxide Leads to damage of endothelium

50. Tissue Mechanics Shear Stress on the Blood Vessels Alters sensitivity of vascular smooth muscle Causes hypertrophy of vascular smooth muscle. Alters lipid and protein synthesis in tunica media

51. Tissue Mechanics How is the Cell “Elasticity” Important? Consider the epidermis… Keritanized stratified squamous epithelium

52. Tissue Mechanics

53. The basal layer must stay adherent to the basement membrane. Elasticity (good cell volume and adequate cell membrane). Thus: cuboidal shape Cell-cell adhesion (surface proteins, cytoskeleton, and interacting structural proteins)

54. Tissue Mechanics The basal layer also needs to remain polarized Cytoskeleton Basement membrane The basal layer needs to decide when to divide Cell-cell interactions Cell-basement membrane interactions Basal Cell Structure is Function!

55. Tissue Mechanics

56. The keritinized layer does not need to be adherent to the basement membrane,..But it does need to be waxy and impermeable

57. Cellular Mechanics Inelastic Poor cell volume, mostly keratin Thus: squamous shape Cell-cell adhesion less necessary Shingle distribution Shedding on Shear Force Squamous Cell Structure is Function!

58. Connective Tissue Extracellular Matrix Fibers Collagen Elastin Reticular Fibers Ground Substance Blood Ultrafiltrate Proteoglycans Glycosaminoglycans

59. Mechanical Properties Fibers give tensile strength and recoil in the direction of the fiber Ground substance gives compressibility and expansion

60. Collagen

61. Elastin

62. Mechanical Properties Slope of the “elastic region” determines whether a fiber provides more resistance or allows more recoil

63. Stress Strain Curve Strain = elongation / equilibrium length Stress = applied force / cross-sectional area

64. Stress Strain Curve Collagen = Lots of stress, minimal elongation Elastin = Stress generates excellent elongation collagen elastin

65. Stress Strain Curve Collagen = Lots of stress, minimal elongation Length of Fibers determine curve Collagen Length y Collagen Length x x yx

66. Proteoglycans Glycosaminoglycan (Hyaluronate) Proteoglycan

67. Stress Strain Curve Elastin, Proteoglycan similar profiles Difference is relative starting point PG elastin

68. Cartilage

69. Hyaline Cartilage

70. Cartilage Architecture

71. Stress Strain Curve Collagen, Proteoglycan different curves PG collagen

72. Stress Strain Curve Total Curve satisfies two different needs: Absorb shocks, Resist tension PG collagen Tissue Curve

73. Stress Strain Curve Total Curve satisfies two different needs: Absorb shocks, Resist tension PG collagen Tissue Curve

74. Cartilage Architecture

75. Bone Architecture Hydroxyapatite in Collagen

76. Bone Architecture Hydroxyapatite in Collagen

77. Stress Strain Curve Hydroxy Apetite Tissue Curve

78. Bone Architecture Hydroxyapatite in Collagen

79. Stress Strain Curve Hydroxy Apetite Tissue Curve collagen

80. Stress Strain Curve Hydroxy Apetite Tissue Curves collagen

81. Bone Cross Section

82. Bone, Thick Slice

83. Bone “Failure”

84. Bone Architecture Concentric arrangement prevents failure from propagating Constant remodeling removes old failures

85. Loose Connective Tissue

86. Dense, Irregular Connective Tissue

87. Dense, Regular Connective Tissue

88. Elastic Connective Tissue

89. Stress Strain Curve Elastin, Proteoglycan similar profiles Difference is relative starting point PG elastin

90. Stress Strain Curve Collagen = Lots of stress, minimal elongation Elastin = Stress generates excellent elongation collagen elastin

91. Stress Strain Curve Collagen = Lots of stress, minimal elongation Elastin = Stress generates excellent elongation collagen elastin

92. Stress Strain Curve Collagen = Lots of stress, minimal elongation Elastin = Stress generates excellent elongation Tissue Curve

93. Cartilage versus Elastic Tissue Cartilage: Elastic curve during compression Elastic Tissue: Elastic curve during stretch

94. Mechanics Questions?