Chapter 5 Membrane Dynamics

8/8/2019 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



Cell Membrane Structure: Fluid Mosaic ModelCell Membrane Structure: Fluid Mosaic Model

Thickness ~ 8nm

PLs

Cholesterol

Proteins: peripheral (associated) or integral



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?



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



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?



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??



Passive Transport

DiffusionDiffusion ± ± 3 types:3 types:

± ± simple diffusionsimple diffusion

± ± osmosisosmosis

± ± facilitated diffusion (= mediated transport)facilitated diffusion (= mediated transport)



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





Cytoskeleton Proteins

anchor membrane proteins



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



Time for diffusion to progress to given

distance ~ to distance squared

diffusion over 100 Qm takes 5 sec.

diffusion over 200 Qm takes ??



Diffusion effective only over shor t distances!

Distance ± Time Relationship



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



Membrane

Proteins

Fig 5-7



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



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)



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



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.)



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)



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



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



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



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



Mechanism of the Na+ /K+-ATPase

start

Fig 5-17



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



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



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?



Glucose and f r uctose use same

trans port pr otein

Saturation of carrier mediated transport:

Competition

andSaturation

Fig 5-18 Fig 20



Table 5-4



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



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)



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



R eceptor Mediated Endocytosis and

Membrane R ecycling

Fig 5-28



3. Exocytosis3. Exocytosis

Intracellular vesicle fuses with membranep

Requires energy (ATP) and Ca2+

Examples: large lipophobic molecule secretion;

receptor inser tion; waste removal



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



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?



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



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



Distribution of Solutes in Body Fluid Compartments

C ompare t o Fig 5-33



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



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



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)



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



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



Osmolar ity and Tonicity

Compar ison

C ompare t o Fig 5-35

A is isosmotic to B A is hypotonic to B



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



Electrical Disequilibrium and

Resting Membrane Potential

(pp.156-163) will be covered at thebeginning of Ch 8





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



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



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



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



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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Chapter 5 Membrane Dynamics