1 Flashcards
What is a cell
Basic unit of life Smallest unit able to
reproduce
Eukaryotic cells
Everything except bacteria
Prokaryotic cells
bacteria cells
What is a tissue
Group of cells plus matrix that have a specific
function
Four main types of tissue
epithelial
connective
muscle
nervous
what is the Extracellular matrix
3D matrix surrounding the cell :
• provides support and structure for cells
• regulates cell function
Van’t Hoff equation -osmotic pressure
tells us that osmotic pressure is proportional to concentration : Π=𝑐𝑅𝑇
Polyelectrolyte
polymer with groups that
dissociate in solvent leaving
charged regions
Proteoglycan function in ecm and how its achieved
Proteoglycans attract and retain water in the ECM
Important for
• filling space
• allowing transport of solutes
• mechanical properties
achieve this by exerting an osmotic pressure
what is a Proteoglycan
core protein chain with GAG “hairs” bonded to it 2 types decorin and aggrecan
Glycosaminoglycans (GAGs)
Polysaccharide chains • Four main groups • Hyaluronan • Chondroitin sulphate & dermatan sulphate • Heparan sulphate • Keratan sulphate
Decorin
A few GAG chains
• Chondroitin and dermatan sulphate
• Role in developing collagen fibres
“decorates” collagen fibers
Aggrecan
100s of GAG chains
Chondroitin and keratan sulphate
Role in providing structure to extracellular matrix
issues with the Van’t Hoff equation
bad for high concentrations and doesnt account for charged molecules
Donnan model - cocentration
semi permeable membrane in a in a jar of solution so some molecules cant make it through impacting the concentration of ions / final distribution of solutes
cell model - concentration
tba
What do aggrecan molecules attach to when they form an aggrecan aggregate
Hyaluronan
which distribution can be used to model the charge density in the rod-in-cell model
Boltzmann
What is the term that describes the contents of a cell (fluid plus organelles)?
Cytoplasm
Why are glycosaminoglycans good at attracting and retaining water in the extracellular matrix?
They have a negative charge
They are fixed in the matrix
Poisson’s equation for electrostatics
𝛻^2𝜓( 𝑟) =−𝜌 (𝑟)/𝜀 𝜌 (𝑟) =𝑧𝑒𝑐 (𝑟) 𝜓 𝑟 Mean electric potential at r 𝜌 𝑟 Mean charge density at r 𝜀 Permittivity of the solution c(r) Ion concentration at r
Diffusivity definition
A measure of how easily a solute diffuses through a medium - diffusion coefficient
Diffusivity equation
⟨ 𝑥^2⟩ =2𝑑𝐷t
𝑑 Number of dimensions
𝐷 Diffusivity
𝑡 Time
Stokes-Einstein equation -diffusivity
𝐷 = 𝑘𝑇/6𝜋𝜇𝑅 𝐷 Diffusivity 𝑘 Boltzmann’s constant 𝑇 Temperature 𝜇 Fluid viscosity 𝑅 Radius of sphere
what scenario does the Stokes-Einstein equation consider
Stokes-Einstein equation
considers a spherical particle with
a no-slip boundary condition
Hydrodynamic radius /Stokes radius
the radius of the molecule as the radius of a
sphere with the same diffusivity
Factors affecting
diffusivity
- Steric exclusion
- Hydrodynamic drag
- Tortuosity
Steric exclusion
when a solute molecule in water has a relatively larger hydrodynamic radius than water leading to a deficiency of the solute molecule in the vicinity of a second solute molecule
Hydrodynamic drag
Fluid drag opposes solute movement
More drag as solute radius increases
Tortuosity equation
𝜏 =𝑙′/𝑙
𝜏 Tortuosity
𝑙 Linear distance
𝑙′ Path length
Reptation
large molecules wiggle through holes
Fick’s first law - diffusion
𝐽 =−𝐷(𝑑𝑐/𝑑𝑥)
J Diffusion flux (amount per unit area
per unit time)
𝐷 Diffusivity
𝑑𝑐/𝑑𝑥 Concentration gradient
Steric partition coefficient
Steric partition coefficient reduces diffusivity and also concentration
𝐶 =𝐾𝐶_0
Fick’s second law - diffuision
𝜕𝑐/𝜕𝑡 =𝐷𝜕^2𝑐/𝜕𝑥^2 c Concentration 𝑡 Time 𝑥 Distance 𝐷 Diffusivity
what does Fick’s first law describe
there is an area of high and an area of low concentration these do not change the flux of solute is constant - calculates the flux
what does Fick’s second law describe
Solute spreads out from source
Concentration changes as a function of time and distance
What causes fluid flow
mechanical or osmotic pressure
Darcy’s law - volume flow ratw
𝑄 =−𝐴𝜅/𝜇 𝑑𝑃/𝑑𝑥 𝑞 =−𝜅/𝜇 𝑑𝑃/𝑑𝑥 𝑄 Volume flow rate 𝑞 Volume flow rate per unit area 𝐴 Cross-sectional area 𝜿 Intrinsic hydraulic conductivity 𝜇 Fluid viscosity 𝑑𝑃/𝑑𝑥 Pressure gradient
what does Darcy’s law describe
describes the flow of a fluid through a porous medium
what is Hydraulic conductivity
Describes how easily water can flow through a porous medium
what affects Hydraulic conductivity
- size of pores
- spatial distribution
- connectivity
Poiseuille equation - Flow along pipe of circular cross section
Flow along pipe of circular cross section 𝑄 =−𝜋𝑟^4/8𝜇 𝑑𝑃/𝑑𝑥 𝑄 Volume flow rate 𝒓 Pipe radius 𝜇 Fluid viscosity 𝑑𝑃/𝑑𝑥 Pressure gradient
Carman-Kozeny equation - hydraulic conductivity
𝜅 =𝜀𝑟^2/𝐺 𝜅 Hydraulic conductivity 𝜺 Fractional void volume 𝑟 Mean hydraulic radius of tubes 𝐺 Kozeny factor
what does the Kozeny factor depend on
depends on channel shape and tortuosity • straight tubes, G = 2 • random orientation, G = 3 – 5 • but also depends on ε • G → 100 as ε→ 1
Poroelasticity
Theory that describes the behaviour of a poroelastic material
• porous elastic solid
• filled with viscous fluid
• interaction between fluid flow and solid deformation
Terzaghi’s theory of effective stress
Load shared between solid and fluid 𝜎 =𝜎∗ +𝑝 𝜎∗ Effective stress 𝑝 Pore pressure 𝜎 Total stress
what happens in terms of the Terzaghi equation at a sealed boundary
all components are constant
what happens in tersm of the Terzaghi equation at a free draining boundary
total stress constant
effective stress increases
pore pressure decreases
what happens to hydraulic concutivity with increaed strain
it decreases
Viscoelasticity
A viscoelastic material has both an elastic and a viscous component to its response
Elastic behaviour
• Apply a force • Material deforms • Remove force • Material reforms to original shape • Energy stored in material and then returned
Viscous behaviour
• Apply a force • Material flows • Remove force • Material remains ‘deformed’ • Energy dissipated and not returned
Hysteresis
• Strain increased then decreased • Stress differs between loading and unloading • Energy lost
Creep
- Constant stress applied
* Strain increases over time
Stress relaxation
- Constant strain applied
* Stress reduces over time
Spring equation
𝜎 =𝐸𝜖
Dashpot equation
𝜎 =𝜂 𝑑𝜖/𝑑𝑡
𝜂 - viscosity
Maxwell model - overview
Spring and dashpot in series
Stress equal in both components
Total strain equals sum of components
Elastic behaviour for sinusoidally varying stress
Elastic behaviour
• Strain in phase with applied stress
• Peak stress at peak strain
Viscoelastic behaviour for sinusoidally varying stress
- Strain lags stress by p/2
* Peak stress at peak strain rate
Storage modulus
elastic behaviour (energy stored) 𝐸′ =𝐸∗cos𝛿
Loss modulus
viscous behaviour (energy dissipated) 𝐸′′ =𝐸∗sin𝛿
what does the loss factor depend on
temperature
hydration
frequency
The stress experienced by the solid part of the material in Terzaghi’s theory
Effective stress
collagen types and uses
Collagen I – tendon, skin, blood vessels, bone
• Collagen II – cartilage
• Collagen III – co-distributed with type I
• Collagen IV – basement membranes
Organisation of collagen
Microfibrils- • Collagen molecules • Tropocollagen • Three polypeptide chain Fibrils- cross-linked in staggered arrangement
Collagen IV in basal lamina
Basal lamina is part of the basement membrane which is alayer of ECM that separates and anchors epithelium to connective tissue the Collagen IV forms sheets
what is Elastin
Elastin
• Elastic fibres
• elastin core (90 % of the fibre)
• sheath of microfibrils (fibrillin)
Formation and assembly of elastin
made in endoplasmic reticulum sent to golgi body transported to membrane sent to ecm hydophobic so clumps together
what does a polymer tend towads in terms of entropy
tends to high entropy state to minimise distance between end (relaxed polymer)
Entropic restoring force
Stretching elastic fibres -> Reduces number of microstates -> Reduces entropy ->Generates restoring force
Fibre composite
one of the materials is in the form of discontinuous fibres embedded in a matrix
Fracture toughness of Fibre composite
A tough material can absorb a lot of energy without breaking
Fibres deflect the crack and energy used to debond the fibres from the matrix
what are Fibre composite properties are dependent on
- quantity of fibres
- orientation of fibres
- Interface between fibre and matrix
- Shape of fibre ends
- Fibre length
Rule of mixture models (fibre composites)
• assume that fibres are aligned, continuous, and attached
perfectly to matrix
• composite properties dependent only on fibre properties, matrix properties, and volume fraction
continous vs short fibre in fibre composite
continous + σ= εE along whole length of fibre
Short fibre:
• ε applied to composite, only matrix experiences ε
What type of cells manufacture collagen
fibroblasts
The efficiency of fibre reinforcement depends on fibre orientation. Which relationship correctly relates the efficiency to the angle the fibres make with the applied load
cos^4
Lipid bilayer description
- Double layer of lipid molecules
- held together by noncovalent bonds
- ~ few nm thick
- lipids are amphiphilic with Hydrophilic polar end and Hydrophobic non-polar end
in a cell the membrane =
walls
in a cell the cytoskelleton =
framework
in a cell the mitochondria =
engines
in a cell the nucleus =
control center
in a cell the Endoplasmic reticulum =
factories
in a cell the Golgi apparatus =
packaging plant
in a cell the Lysosomes =
waste disposal
how do we know the lipid layer is two molecules thick
Gorter & Grendel, 1925 - extracted lipids from red blood cells and found a surface area to no of lipds to be ~2
in what ways is the bilayer fluid
lateral diffusion , flip flop, flexion of tails, torsion
what does the fluidity of the lipid bilayer depend on
- length of fatty acid chains
- kinks in fatty acid chains
- cholesterol
- protein concentration
impact of cholesterol on phospholipids (fluidity)
reduce fluidity by stiffening regions between phospholipids
increase fluidity by reducing packing between phospholipids
Surface tension measurement using a Wilhelmy plate
𝛾 = 𝐹/𝐿cos𝜃 𝛾 Surface tension 𝐹 Measured force 𝐿 Wetted length (2d + 2w) 𝜃 Contact angle
what is Surface pressure as a function of area trend for lipids
falls off with increased area
Membrane protein functions (6)
inter cellular joinings, emzyme activity, transport, cell cell recognition, anchorage, signal transduction
Integrins - definition
Integrins are a large family of cell adhesion proteins
intergrins functions
- relay signals about matrix
- cell migration
- matrix assembly
Glycocalyx - definition
Layer on the external surface of cells - sugat coat
Glycocalyx functionss
- barrier
* mechanical sensor
Passive transport - def and 2 mechanisms
Molecules transported down electrochemical gradient • No energy required 2 mechanisms • simple diffusion • facilitated diffusion
Fick’s law for simple (passive) difusion
Small non-polar molecules diffuse across cell membrane Q=−ADdc/dx Q Diffusion flux (amount per unit time) 𝐴 Membrane area 𝐷 Diffusivity 𝑑𝑐/𝑑𝑥 Concentration gradient
Channel proteins
Allows solutes to cross without touching the membrane
Can be always open or gated
Carrier proteins
Specific to solute but doesn’t always need solute to change state
Allows solutes to cross without touching the membrane
Transition occurs randomly and is reversible
Active transport
Active transport • Molecules transported against electrochemical concentration gradient • Energy is required to perform the transport • Protein pumps
Vesicle transport
Vesicles are formed from small sections of membrane
• They transport substances
• within a cell (between organelles)
• in and out of the cell
what is the cytoskeleton made of
microtubules, actin filaments, and intermediate filaments
what is an actin filament
Actin filaments (F-actin) are linear polymer chains of globular
actin (G-actin) they shrink and grow by attachment and detachment at ends
Minus end is pointed
Plus end is barbed
Polymerisation (more complicated) description
G-actin in two different forms (rates not identical)
Rate constants higher at the plus end
Treadmilling of polymer
Number of monomers in the filament is constant Filament ‘moves’
what is a Microtubule
Microtubules are tubular polymers of globular tubulin
Similar to actin
• has a ‘plus’ and ‘minus’ end
• can grow and shrink
what is a Intermediate filament
- Intertwined fibrous proteins forming protofilament
* 8 protofilaments arranged to form filament
Cytoskeleton functions
Actin filaments • cell shape • cell movement Microtubules • organelle organisation • cell division • transport within the cell Intermediate filaments • mechanical strength
Cell migration description
- Protrusion at front -polymerisation of actin pushes on membrane
- Attachment to surface atfront
- Retraction at rear as cell moves
- De-attachment fromsurface at rear- actin forms part of contractile assembly to pull cell
micro tubules during cell division
all connected to one point in cell and pull chromosomes apart
Persistence length def
the length of a polymer under wich it acts like a stiff rod
Persistence length equation
ξ= 𝐸𝐼/𝑘𝐵𝑇 ξ Persistence length 𝐸𝐼 Bending stiffness 𝑘𝐵 Boltzmann’s constant 𝑇 Temperature
Order the cytoskeleton components by their diameter from smallest at the top to largest at the bottom.
Actin filaments
Intermediate fibres
micro tubules
Fluctuation
spectroscopy description
Contour of cell determined
Analysed using Fourier series
• mean square amplitude for each
mode
Micropipette aspiration description
• Micropipette (1 – 10 mico m ø)
brought into contact with membrane
• Negative pressure applied
• Cell sucked into micropipette (observed with microscope)
• Length measured as function of pressure
Liquid drop model and Laplace pressure equation
∆𝑃 =𝑃𝑖𝑛 −𝑃𝑜𝑢𝑡 =2𝛾/𝑅 ∆𝑃 Pressure difference 𝛾 Surface tension 𝑅 Radius 𝛾=RcRcap(Pp-Pa)/2(Rcap-Rc)
Optical tweezers
Light beam with higher intensity at centre
F=-kx
Atomic Force Microscope (AFM)
Tip interacts with sample
Attractive/repulsive forces cause cantilever to bend
Bending monitored by reflected laser light
Properties of the cell determined from the force and the deflection
tapping mode gentler for cells
Mechanotransduction definition
Cells sense physical forces and translate them into biochemical or biological responses
External stimulus -> internal response
Mechanotransduction Process
Receive stimulus
Transmit stimulus
Respond to stimulus
3 Receptors of Mechanotransduction
Stretch activated ion channels
intergrins
enzyme linked cell surface receptors
Stretch activated ion channels description - mechanotransduction
Membrane stretching pulls the channel open
somtimes the channel is teathered to the cytoskelenton
somtimes attached to a mechano supportive protein
Integrin def
transmembrane receptors that facilitate cell-cell and cell-extracellular matrix adhesion
2 methods of Mechanotransduction
cytoskeleton, biochemical messenger
Mechanotransduction response from cell
cytoskeleton -> DNA to RNA -> endoplasmic reticulum ->gogli ->protein->target
Three types of cartilage
- hyaline
- fibrocartilage
- elastic
Articular cartilage desctription
- Type of hyaline cartilage
- Located within synovial joints
- Covers articular surfaces
- ~ a few mm thick
Collagen fibril arrangement for cartilage
Parallel fibres
Resist shear forces at surface
Perpendicular fibres
Tether cartilage to bone
Cell nutrition and waste products for cartilage
Avascular (no blood supply)
• Cells receive nutrients and get rid of waste products via
• capillaries in underlying bone
• surrounding synovial fluid
Mechanisms
• diffusion
• convective transport from fluid movement
Mechanical functions of cartilage
- Supports and distributes load
* Provides low friction surface
cartilage components
Collagen fibrils and Proteoglycan gel
osteoarthritis
most common form of arthritis, It occurs when the protective cartilage that cushions the ends of the bones wears down over time
initial roughening → complete loss of cartilage
-primary
-secondary (triggered by injury)
cartilage degradation with reference to changes in the extracellular matrix and cells
Changes in the ECM • Collagen and proteoglycans degraded • split into smaller units • Collagen • reduced ability to reinforce matrix • Proteoglycans • increased ability to leave the matrix
Boundary layer lubrication
Proteoglycans coat the cartilage surface
They form a mucous, slippery boundary layer
Hydrodynamic lubrication
- Surfaces moving past each other
- Fluid dragged between them
- Pressure generated
State the function of tendons and ligaments in the musculoskeletal system
Tendon • connects muscle to bone • transfers forces from muscles Ligament • connects bone to bone • limits/controls movement
functional requirements of tendons and ligaments
Tendons need to be stiff for effective force transfer
Tendons need to be flexible to wrap around joints
Ligaments need to be stiff to limit movement whilst still allowing some motion
Strong-doesn’t break (tendon and ligament)
Flexible-accommodate joint angles and motion (tendon and ligament)
composition and structure of tendons and ligaments
water, collagen and elastin
Structure - collagen - fibril - fibre - fasicle - tendon/ligament
Fibril structure
Fibril 10-100 nm
Staggered arrangement of cross-linked
molecules with D period ~ 67 nm
Fibre structure
is crimped
Fascicle and tendon structure
- ECM within and around fascicles
- space for cells and blood vessels
- lubrication for sliding of fascicles
Toe region for collagen in tendons/ligaments
Toe region
• Collagen fibre crimp stretches out
• Collagen fibres align
Linear region for collagen in tendons/ligaments
- Collagen fibres un-crimped and aligned
- Fully supporting load in tissue
- Young’s modulus from this region
Bone functions
Mechanical • support • protection • movement Storage • minerals Production • blood cells
Bone types
Cortical bone (also called compact or dense bone) Cancellous bone(also called trabecular or spongy bone)
Bone structure - cortical bone
osteon and lamella
mineralised collagen fibres
collagen/ mineral composite
crystal latice
Bone structure - tribecular bone
trabecular packet and lamella
mineralised collagen fibres
collagen/ mineral composite
alpha chains
Wolff’s law
Bone adapts in response to mechanical stress
function of the osteoblasts in bone remodelling
build bone -synthesize bone matrix and coordinate the mineralization of the skeleton
function of the osteoclast in bone remodelling
removes/ breaks down old bone by excreeting acid and enzmes, calcium traveles through the cell and is released, degraded matrix is removed by vesicle transport, adhesion proteins seal cell to bone matrix, ruffled border provides a large surface area
function of the osteocytes in bone remodelling
orchestrates bone remodelling, are embedded in bone matrix and recieves info from strain in solid matrix and sheer stress from fluid flow
characteristics of osteoporosis
Condition involving reduction in bone tissue
• More resorption than building
Muscle structure
myofibril
singular muscle fibre (cell)
fascicle (bound in connective tissue)
muscle (nerves and blood vessels throughout
myofibril
2 interdigitating strucures - actin (thin) filaments and myosin (thick) filaments
sliding filament theory
describes the mechanism that allows muscles to contract. According to this theory, myosin (a motor protein) binds to actin. The myosin then alters its configuration, resulting in a “stroke” that pulls on the actin filament and causes it to slide across the myosin filament
Cross-bridge cycling - sliding filament theory
Cross-bridge formation
Power stroke
Cross-bridge detachment
Reactivation of myosin head
Muscle force equation
𝐹 =𝐴×𝑇
𝐴 Cross-sectional area
𝑇 Specific tension of muscle
(can also use Physiological cross-sectional area)
Physiological cross-sectional area equation
𝑃𝐶𝑆𝐴=𝑉𝑚/𝐿𝑓
𝑉𝑚 Muscle volume
𝐿𝑓 Muscle fibre length
Muscle force fibre angle equation
𝐹𝑚𝑢𝑠𝑐𝑙𝑒 =𝐹𝑓𝑖𝑏𝑟𝑒𝑠 cos𝜃
𝐹𝑚𝑢𝑠𝑐𝑙𝑒 Force muscle is able to apply along mechanical axis
𝜃 Angle of fibres with respect to mechanical axis
Cardiovascular system Primary function
transport system for oxygen, nutrients, waste products
Blood vessel types
Artery • wide and long • few in number Capillary • narrow and short • many in number
Blood Vessel structure
Tunica externa Tunica media (larger for arteries) Tunica intima
Tunica externa
- Loose network of collagen
* Tethers vessel to surrounding tissue
Tunica media
• Smooth muscle cells plus collagen and elastic fibres
• Elasticity and strength (and contractility in smaller vessels)
less in veins as arteries need it to move blood along
Tunica intima
• Endothelial cells on a layer of connective tissue
• Physical and chemical barrier
Basement membrane after it
glycocalax of endothelial cells
endothelial cells have a very thick glycocalax
Capillary structure
Glycocalyx -inner
Endothelial layer
Basement membrane -outer
oedema + causes
fluid retention
Oedema is usually caused by
standing or sitting in the same position for too long
eating too much salty food
being overweight
being pregnant
aking certain medicines
Oedema can also be caused by:
an injury
problems with your kidneys, liver or heart
a blood clot
an infectionshape of a blood cell and explain how it can travel along very small capillaries
Biconcave disc
deformes to Slipper and then parachute to fit
key difference in the cytoskeleton of the blood cell compared to other cells
have spectrin filaments connectedby actin to membrane proteins
key points of the Human Tissue Act 2004
regulates the removal, storage and use of human tissue
what can we use to Repair and replace
We can use tissue from
• patient’s own body
• another human
• another species
Problems with Repair and replace
Compatibility of tissue or artificial material used for repair or
replacement
Stress shielding problem
Implant is stiffer than bone
leads to the reduction in bone density
