Download Cellular Mechanics

Cellular and Tissue
Mechanics
Jim Pierce
Bi 145a
Lecture 4, 2009-2010
Cellular Mechanics
Cell Physiology is really
the study of cellular mechanics.
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.
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
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!
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
Mechanics
• Types of Loads:
Mechanics
Bending
• Combined
Loads
Twisting
Material Properties
• How does the material respond to Load?
• Strength
• Resilience
• Toughness
• Elastic
• Plastic
• Failure
Stress Strain Curve
• Strain = elongation / equilibrium length
• Stress = applied force / cross-sectional area
Stress Strain Curve
• Elastic – When a Load (Strain) results in a
linear stress profile
(example = spring)
Stress Strain Curve
• Yield Point – The Load that cannot be elastically
absorbed. (i.e. the material absorbs load)
Stress Strain Curve
• Failure – When the load ultimately breaks
the material
(hence ultimate strain)
Failure
Stress Strain Curve
• Plastic – when a load deforms a material and
changes the structure of the material
Stress Strain Curve
Volume
Volume
Pressure
• Similar to Pressure-Volume Curve
• Area = Work
Stress Strain Curve
• Resilience = area of elastic region
• Toughness = area of elastic and plastic regions
Stress Strain Curve
Starting
Point
• “Shock Absorber”
Stress Strain Curve
Starting
Point
• “Resilient Connector”
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
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
Fluid Mechanics
• How do we describe a fluid
and its environment?
•
•
•
•
Pressure and Volume
Velocity and Flow
Density
Viscosity
• Types of Flow
• Compressibility
Fluid Mechanics
• Viscosity – how much you put into it
versus how much you get out of it
Fluid Mechanics
• Viscosity = slope of stress / strain
Fluid Mechanics
• Viscosity
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:
Fluid
Mechanics
Turbulent
Flow
Fluid
Mechanics
Laminar
Flow
Cellular Mechanics
• A cell has membrane properties
•
•
•
•
Surface Tension
Membrane Conductance
Membrane Capacitance
Adhesion Tendancy
• Membranes are well discussed
in Bi/CNS 150
Cellular Mechanics
• Loading the Cell
• Consider the Erythrocyte
• Stress (Scalar)
• Strain Forces
• Compression / Expansion
• Shear Forces
• Membrane Tension and Elasticity
Cellular
Mechanics
Red Cell Membrane
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)
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)
Cellular Mechanics
• Thus, Sickle Cell Anemia is a
Hemolytic Anemia!
• (so are most hemolytic anemias)
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.
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.
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
Cellular Mechanics
Movie by Steven House, PhD
During his fellowship at Columbia
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!
Cell Examples
• Primary sensory neurons in the dermis
• Merkel cell of epidermis (touch sensor)
• Serosal Cell of the body cavities
• Transitional Epithelium
Skin and the Nervous System
Merkel Cell
• Unknown origin
(Likely Neural Crest)
• Embedded in
Epidermis
• Light Touch
Pacini Corpusle
Pacini Corpusle
• Neural Crest origin
• Bipolar
Sensory Neuron
• Located in Dermis
• Deep touch
Hair Sensation
• Free neuron
• Attached to
base of hair
• Hair movement
Serosa
Serosa
• Derived from
intraembryonic
coelome
• Lines the
body cavities
Transitional Epithelium
• Lines the bladder
Relaxed
Contracted
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
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
Tissue Mechanics
• How is the Cell “Elasticity” Important?
• Consider the epidermis…
• Keritanized stratified squamous epithelium
Tissue Mechanics
Tissue Mechanics
• 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)
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!
Tissue Mechanics
Tissue Mechanics
• The keritinized layer does not need
to be adherent to the basement membrane,
• ..But it does need to be waxy
and impermeable
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!
Connective Tissue
• Extracellular Matrix
• Fibers
• Collagen
• Elastin
• Reticular Fibers
• Ground Substance
• Blood Ultrafiltrate
• Proteoglycans
• Glycosaminoglycans
Mechanical Properties
• Fibers give tensile strength and recoil
in the direction of the fiber
• Ground substance gives
compressibility and expansion
Collagen
Elastin
Mechanical Properties
Slope of the “elastic region” determines
whether a fiber provides more resistance
or allows more recoil
Stress Strain Curve
• Strain = elongation / equilibrium length
• Stress = applied force / cross-sectional area
Stress Strain Curve
collagen
elastin
• Collagen = Lots of stress, minimal elongation
• Elastin = Stress generates excellent elongation
Stress Strain Curve
Collagen
Length x
x
Collagen
Length y
yx
• Collagen = Lots of stress, minimal elongation
• Length of Fibers determine curve
Proteoglycans
Glycosaminoglycan
(Hyaluronate)
Proteoglycan
Stress Strain Curve
elastin
PG
• Elastin, Proteoglycan similar profiles
• Difference is relative starting point
Cartilage
Hyaline Cartilage
Cartilage Architecture
Stress Strain Curve
collagen
PG
• Collagen, Proteoglycan different curves
Stress Strain Curve
Tissue Curve
collagen
PG
• Total Curve satisfies two different needs:
• Absorb shocks, Resist tension
Stress Strain Curve
Tissue Curve
collagen
PG
• Total Curve satisfies two different needs:
• Absorb shocks, Resist tension
Cartilage Architecture
Bone Architecture
Hydroxyapatite in Collagen
Bone Architecture
Hydroxyapatite in Collagen
Stress Strain Curve
Hydroxy
Apetite
Tissue
Curve
Bone Architecture
Hydroxyapatite in Collagen
Stress Strain Curve
Hydroxy
Apetite
Tissue
Curve
collagen
Stress Strain Curve
Hydroxy
Apetite
Tissue
Curves
collagen
Bone Cross Section
Bone, Thick Slice
Bone “Failure”
Bone Architecture
• Concentric arrangement prevents
failure from propagating
• Constant remodeling removes
old failures
Loose Connective Tissue
Dense, Irregular
Connective Tissue
Dense, Regular
Connective Tissue
Elastic Connective Tissue
Stress Strain Curve
elastin
PG
• Elastin, Proteoglycan similar profiles
• Difference is relative starting point
Stress Strain Curve
collagen
elastin
• Collagen = Lots of stress, minimal elongation
• Elastin = Stress generates excellent elongation
Stress Strain Curve
collagen
elastin
• Collagen = Lots of stress, minimal elongation
• Elastin = Stress generates excellent elongation
Stress Strain Curve
Tissue
Curve
• Collagen = Lots of stress, minimal elongation
• Elastin = Stress generates excellent elongation
Cartilage versus Elastic Tissue
• Cartilage:
Elastic curve during compression
• Elastic Tissue:
Elastic curve during stretch
Mechanics
• Questions?