chapter 5 membrane dynamics
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MembraneMembrane ± ±2 Meanings! 2 Meanings!
Epithelial membranesEpithelial membranes
vs.vs.
Cell membranes andCell membranes andMembranes around organellesMembranes around organelles
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Cell Membrane Structure: Fluid Mosaic ModelCell Membrane Structure: Fluid Mosaic Model
Thickness ~ 8nm
PLs
Cholesterol
Proteins: peripheral (associated) or integral
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Membrane Structure: Protein to
Lipid Ratio var ies from cell type tocell type
Ratio for cells with high metabolic activity?Ratio for cells with high metabolic activity?
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Membrane ProteinsMembrane Proteins
IntegralIntegral
((MembraneMembrane--spanningspanning
or intr insicor intr insic)) Can span membraneCan span membrane
several timesseveral times
Either move around or Either move around or are kept in place byare kept in place bycytoskeleton proteinscytoskeleton proteins
Allows for cell polarity Allows for cell polarity
AssociatedAssociated
(per ipheral or (per ipheral or extr insic)extr insic)
Loosely bound toLoosely bound to
membranemembrane
Enzymes andEnzymes and
structural proteinsstructural proteins
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Other Phospholipid Behaviors inOther Phospholipid Behaviors in
HH22O:O:
Phosphol ipid bi l ayer Phosphol ipid bi l ayer
MicelleMicelle ± ± Role in digestion andRole in digestion and
absor ption of fats in GIabsor ption of fats in GI
tracttract
LiposomeLiposome ± ± Larger, bilayer, hollowLarger, bilayer, hollow
center with aqueous corecenter with aqueous coreC l inical rel evance?
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Movement across MembraneMovement across Membrane
Membrane permeability var ies for Membrane permeability var ies for
different different moleculesmolecules && cell typescell types
Tw o movement categ ories:Tw o movement categ ories:
PassivePassive andand
ActiveActive
depends on??
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Passive Transport
DiffusionDiffusion ± ± 3 types:3 types:
± ± simple diffusionsimple diffusion
± ± osmosisosmosis
± ± facilitated diffusion (= mediated transport)facilitated diffusion (= mediated transport)
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Active Transpor tActive Transpor t
Always proteinAlways protein--mediatedmediated ± ± 3 types:3 types:
coco--transpor ttranspor t
vesicular transpor tvesicular transpor t
receptor mediated transpor treceptor mediated transpor t
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Cytoskeleton Proteins
anchor membrane proteins
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Diffusion Process (Passive)
Fig 5-5
Uses energy of concentrationUses energy of concentration
gradientgradient
Net movement until state of Net movement until state of
equilibr ium reached (no moreequilibr ium reached (no more
conc. gradient)conc. gradient)Direct correlation to temperatureDirect correlation to temperature
(why?)(why?)
Indirect correlation to moleculeIndirect correlation to molecule
sizesize
Slower with increasing distanceSlower with increasing distanceLipophilic molecules can difuseLipophilic molecules can difuse
through the phospholipid bilayer through the phospholipid bilayer
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Time for diffusion to progress to given
distance ~ to distance squared
diffusion over 100 Qm takes 5 sec.
diffusion over 200 Qm takes ??
diffusion over 400 Qm takes ??
diffusion over 800 Qm takes ??
Diffusion effective only over shor t distances!
Distance ± Time Relationship
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Fick¶s law of Diffusion (p 135)
surface area x conc. gradient
membrane resistance x membrane thickness
rate of
diffusion=
depends on
siz e and l i pid-solubil ity of molecule and
composition of l i pid bila yer
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Membrane
Proteins
Fig 5-7
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Protein-
Mediated Transport
More selectiveMore selective ± ± Active or Passive Active or Passive
Membrane ProteinsMembrane Proteins ± ± StructuralStructural
± ± EnzymesEnzymes
± ± ReceptorsReceptors
± ± Transporters (allows Specificity,Transporters (allows Specificity,Competition, Saturation p 145)Competition, Saturation p 145) ChannelChannel
GatedGated
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Transpor tersTranspor ters
Cell Membrane Regulates Exchange with Cell Membrane Regulates Exchange with
EnvironmentEnvironment
Many molecules use transpor ters to crossMany molecules use transpor ters to cross
cell membrane.cell membrane. W hy? W hy? Exampl es ? Exampl es ?
Two categor ies of transpor ter proteinsTwo categor ies of transpor ter proteins
1.1. Channel proteinsChannel proteins (rapid but not as(rapid but not as
selectiveselective ± ± for small molecules only, e.g.,for small molecules only, e.g.,
water and ions)water and ions)
2.2. Carr ier proteinsCarr ier proteins (slower but ver y (slower but ver y
selectiveselective ± ± also works for large molecules)also works for large molecules)
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1. Channel Proteins1. Channel Proteins
For small moleculesFor small moleculessuch as ??such as ??
Aquapor in; plus > 100Aquapor in; plus > 100
ion channelsion channels
Selectivity based on sizeSelectivity based on size
& charge of molecule& charge of molecule
All have gate regionAll have gate region
± ± OpenOpen
± ± GatedGated
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Open Channels vs.Open Channels vs. Gated ChannelsGated Channels
= pores= pores
Have gates, but gates areHave gates, but gates areopen most of the time.open most of the time.
Also referred to as ³leakAlso referred to as ³leak
channels´.channels´.
Gates closed most of the timeGates closed most of the time
Chemically gated channelsChemically gated channels(controlled by messenger molecule or (controlled by messenger molecule or ligand)ligand)
Voltage gated channelsVoltage gated channels(controlled by electrical state of cell)(controlled by electrical state of cell)
Mechanically gatedMechanically gatedchannelschannels (controlled by physical(controlled by physicalstate of cell: temp.; stretching of cellstate of cell: temp.; stretching of cellmembrane etc.)membrane etc.)
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2. Carr ier Proteins2. Carr ier Proteins
Never form direct connectionNever form direct connectionbetween ECF and ICFbetween ECF and ICF ± ± 2 gates!2 gates!
Bind molecules and changeBind molecules and changeconformationconformation
Used for small organicUsed for small organicmoleculesmolecules ( suc h as?)( suc h as?)
Ions may use channels or Ions may use channels or carr ierscarr iers
Rel. slow (1,000 to 1 Mio / sec)Rel. slow (1,000 to 1 Mio / sec)
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Cotranspor tCotranspor t
Sympor tSympor t Molecules are carr iedMolecules are carr iedin same directionin same direction
Examples: GlucoseExamples: Glucoseand Naand Na++
Antipor tAntipor t Molecules are carr iedMolecules are carr ied
in opposite directionin opposite direction
Examples: NaExamples: Na++ /K /K++
pumppump
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Facilitated DiffusionFacilitated Diffusion (as a form(as a form
of carr ier mediated transpor t)of carr ier mediated transpor t)
Some character istics same as simpleSome character istics same as simple
diffusiondiffusion
but al so:but al so:
specif icityspecif icity
competitioncompetition
saturationsaturation
Fig s 5-18/20
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Active Transpor tActive Transpor t Movement from low conc.Movement from low conc.
to high conc.to high conc.
ATP neededATP needed
Creates state of Creates state of
disdisequilibr iumequilibr ium
11oo (direct) active transpor t (direct) active transpor t ± ±
ATPases or ³pumpsATPases or ³pumps´ (unipor t ´ (unipor t and antipor t)and antipor t)± ± examples? examples?
22oo (indirect) active(indirect) active
transpor ttranspor t ± ± Sympor t and antipor tSympor t and antipor t
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11oo (Direct) Active Transpor t (Direct) Active Transpor t
ATP energy directly fuels transpor tATP energy directly fuels transpor t
Most impor tant example: NaMost impor tant example: Na++ /K /K++ pump = sodiumpump = sodium--
potassium ATPasepotassium ATPase (uses up to 30% of cell¶s ATP)(uses up to 30% of cell¶s ATP)
Establishes Na+ conc.Establishes Na+ conc.
gradient gradient EEpot.pot. cancan
be harnessed for be harnessed for
other cell functionsother cell functions
ECF: high
[Na+], low [K +]ICF: high [K +],
low [Na+]
Fig 5-16
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Mechanism of the Na+ /K+-ATPase
start
Fig 5-17
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22
oo
(Indirect) Active Transpor t (Indirect) Active Transpor t Indirect ATP use:Indirect ATP use: usesuses
EEpot.pot. stored instored inconcentration gradientconcentration gradient (of (of NaNa++ and Kand K++))
Coupling of ECoupling of Ekinkin of oneof onemolecule with movement molecule with movement of another moleculeof another molecule
Example: NaExample: Na++
/ Glucose / Glucosesympor ter sympor ter
± ± other examplesother examples
2 mechanisms for Glucose2 mechanisms for Glucose
transpor ttranspor t
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Body Fluid Compar tmentsBody Fluid Compar tments
IC fluidIC fluid EC fluidEC fluid
Interstitial fluidInterstitial fluid plasmaplasma
Relatively f r ee exchange
Exchange
much mor e
selective;
Wh y ?
Fig 5-13
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Body Fluid Compartments:
ECF ICF
Critical
Thinking
Question
What pr operties should a molecule have to be used as mark er for
one of the fluid compartments?
Do total H2O; total EC and plasma. Then, how do you f igur e out
ICF and interstitial fluid?
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Glucose and f r uctose use same
trans port pr otein
Saturation of carrier mediated transport:
Competition
andSaturation
Fig 5-18 Fig 20
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Table 5-4
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Vesicular Transpor tVesicular Transpor tMovement of Movement of macromoleculesmacromolecules across cellacross cell
membrane:membrane:
1.1. Phagocytosis (specialized cells only)Phagocytosis (specialized cells only)
2.2. EndocytosisEndocytosis ± ± PinocytosisPinocytosis
± ± Receptor mediated endocytosisReceptor mediated endocytosis
± ± (Caveolae) Potocytosis(Caveolae) Potocytosis
3.3. ExocytosisExocytosis
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1. Phagocytosis1. Phagocytosis
Requires energy Requires energy
Cell engulfs par ticle into vesicle viaCell engulfs par ticle into vesicle via
pseudopodia formationpseudopodia formation
E.g.:E.g.: some WBCssome WBCs engulf bacter iaengulf bacter ia
Vesicles formed are much larger than thoseVesicles formed are much larger than those
formed by endocytosisformed by endocytosis
Phagosome fuses with lysosomesPhagosome fuses with lysosomes ? ? ( see Fig.( see Fig.
5 5- -23)23)
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2. Endocytosis2. Endocytosis
Requires energy Requires energy
No pseudopodiaNo pseudopodia -- Membrane surface indentsMembrane surface indents
Smaller vesiclesSmaller vesicles
Nonselective:Nonselective: PinocytosisPinocytosis for fluids & dissolvedfor fluids & dissolvedsubstancessubstances
Selective:Selective: ± ± Receptor Mediated EndocytosisReceptor Mediated Endocytosis via clathr invia clathr in--coated pitscoated pits --
Example: LDL cholesterol andExample: LDL cholesterol and FamilialFamilialHypercholesterolemiaHypercholesterolemia
± ± PodocytosisPodocytosis via caveolaevia caveolae Fig 5-24
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R eceptor Mediated Endocytosis and
Membrane R ecycling
Fig 5-28
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3. Exocytosis3. Exocytosis
Intracellular vesicle fuses with membranep
Requires energy (ATP) and Ca2+
Examples: large lipophobic molecule secretion;
receptor inser tion; waste removal
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Movement through Epithelia:Movement through Epithelia:
Transepithelial transpor t
Uses combination of active and passive transpor tUses combination of active and passive transpor t
Molecule must Molecule must cross twocross twophospholipidphospholipidbilayersbilayers
Apical and basolateral cell membranes have different Apical and basolateral cell membranes have different proteinsproteins::NaNa++-- glucose transpor ter on apical membraneglucose transpor ter on apical membraneNaNa++ /K /K++--ATPase only on basolateral membraneATPase only on basolateral membrane Fig 5-26
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Transepithelial Transpor t of Glucose
basolateral
apical
1. Na+ /Glucosesymporter only found
on apical side
2. Na+
/K+
-ATPase onlyfound on basolateral
side
3. Facilitated diffusion
C oncept check:A pply Oua bain to either side of cell, what ha ppens?
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Transcytosis
EndocytosisEndocytosis pp vesicular transpor t vesicular transpor t ppexocytosisexocytosis
Moves large proteins intactMoves large proteins intact
Examples:Examples: ± ± Absorption of maternal Absorption of maternal
antibodies fromantibodies frombreast milkbreast milk
± ± Movement of proteinsMovement of proteinsacross capillaryacross capillaryendotheliumendothelium
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Distr ibution of Solutes in Body
Depends onDepends on
selective permeability of cell membraneselective permeability of cell membrane
transpor t mechanisms availabletranspor t mechanisms available
Water is in osmotic equilibr ium (freeWater is in osmotic equilibr ium (freemovement across membranes)movement across membranes)
Ions and most solutes are in chemicalIons and most solutes are in chemicaldisequilibr ium (e.g., Nadisequilibr ium (e.g., Na--K ATPase Pump)K ATPase Pump)
Electr ical disequilibr ium between ECF andElectr ical disequilibr ium between ECF andICFICF
Fig 5-33
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Distribution of Solutes in Body Fluid Compartments
C ompare t o Fig 5-33
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Osmosis
Movement of w ater down itsconcentration gradient.
Osmotic
pressure
Opposes
movement
of water
acrossmembrane
Water moves freely in body until osmotic
equilibr ium is reached
Compare t o Fig . 5-29
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Molarity vs.
Osmolarity
In chemi st ry :In chemi st ry :
Mole / LMole / L
Avogadro¶s # / L Avogadro¶s # / L
In Phy si ol og y In Phy si ol og y
Important is not # of Important is not # of
molecules / L butmolecules / L but# of particles / L: osmol/L# of particles / L: osmol/L
or OsMor OsM
W hy?W hy?
Osmolar ity takes into account dissociation (solubility) of molecules
in solution
Osmolality = OsM/Kg of sol¶n
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Conver t Molar ity to Osmolar ity
Osmolar ity = # of par ticles / L of solutionOsmolar ity = # of par ticles / L of solution
1 M glucose = 1 OsM glucose1 M glucose = 1 OsM glucose
1 M NaCl = 2 OsM NaCl1 M NaCl = 2 OsM NaCl
1 M MgCl1 M MgCl22 = 3 OsM MgCl= 3 OsM MgCl22
Osmolar ity of human body ~ 300 mOsMOsmolar ity of human body ~ 300 mOsM
Compare isosmotic, hyperosmotic, hyposmotic (p Compare isosmotic, hyperosmotic, hyposmotic (p 156)156)
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Tonicity
Physiological term descr ibing howPhysiological term descr ibing howcell volume changes if cell placed incell volume changes if cell placed inthe solutionthe solution
Always comparative. Has no units.Always comparative. Has no units.
± ± Isotonic sol¶n = No change in cellIsotonic sol¶n = No change in cell
± ± Hyper tonic sol¶n = cell shr inksHyper tonic sol¶n = cell shr inks
± ± Hypotonic = cell expandsHypotonic = cell expands
Depends not just on osmolar ity but Depends not just on osmolar ity but onon nature of solutes and permeability nature of solutes and permeability of membraneof membrane
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Penetrating vs. Nonpenetrating
Solutes Penetrating solute: can enter cellPenetrating solute: can enter cell
(glucose, urea)(glucose, urea)
Nonpenetrating solutes: cannot enter Nonpenetrating solutes: cannot enter cell (sucrose, NaCl*)cell (sucrose, NaCl*)
Determine relative conc. of Determine relative conc. of nonpenetrating solutes in solution andnonpenetrating solutes in solution and
in cell to determine tonicity.in cell to determine tonicity. ± ± Water will move to dilute nonpenetrating solutesWater will move to dilute nonpenetrating solutes ± ± Penetrating solutes will distr ibute to equilibr iumPenetrating solutes will distr ibute to equilibr ium
Fig 5-30
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Osmolar ity and Tonicity
Compar ison
C ompare t o Fig 5-35
A is isosmotic to B A is hypotonic to B
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IV Fluid Therapy
2 different purposes:2 different purposes:
± ± Get fluid into dehydrated cells or Get fluid into dehydrated cells or
± ± Keep fluid in extraKeep fluid in extra--cellular compar tmentcellular compar tment
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Electrical Disequilibrium and
Resting Membrane Potential
(pp.156-163) will be covered at thebeginning of Ch 8
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Which of the following is a way for solutes
in a aqueous solution to move from an
area of high solute concentration to anarea of low solute concentration?
A. A. Facilitated diffusionFacilitated diffusionB.B. OsmosisOsmosis
C.C. Active transport Active transport
D.D. A and B A and B
E.E. None of theseNone of these
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Which of the following defines the
term specificity?
A. movement of molecules by the use of
vesicles
B. the energy required to movemolecules
C. a group of carr ier proteins operating
at their maximum rate
D. carr ier transpor t of a group of closely
related molecules
E. none of these
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Water will always move from
___________ situations to _______
situations.
A. A. Hyperosmotic, hyposmoticHyperosmotic, hyposmoticB.B. Hyposmotic, hyperosmoticHyposmotic, hyperosmotic
C.C. Hyposmotic, isosmoticHyposmotic, isosmotic
D.D. Hyperosmotic, isosmoticHyperosmotic, isosmotic
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Which of the following pairs of molecular
characteristics favors diffusion through
the cell membrane?
A. A. Large, polar Large, polar B.B. Large, nonLarge, non--polar polar
C.C. Small, polar Small, polar
D.D. Small, nonSmall, non--polar polar
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Which of the following is a way for solutes
in a aqueous solution to move from an
area of high solute concentration to anarea of low solute concentration?
A. A. Facilitated diffusionFacilitated diffusionB.B. OsmosisOsmosis
C.C. Active transport Active transport
D.D. A and B A and B
E.E. None of theseNone of these