Ch 5: Membrane Dynamics

Law of Mass Balance• Most simply, ins =outs• Homeostasis is notthe same asequilibrium– E.g., membranepotentials

Membrane –2 Meanings!• Epithelial membranesvs.• Cell membranes andMembranes around organelles

Thickness ~ 8nmCell Membrane Structure: Fluid Mosaic ModelPLsCholesterolProteins: peripheral (associated) or integral

Membrane Structure: Protein toLipid Ratio varies from cell type tocell typeRatio for cells with high metabolic activity?

Membrane ProteinsIntegral(Membrane-spanningor intrinsic)• Can span membraneseveral times• Either move around orare kept in place bycytoskeleton proteinsAllows for cell polarityAssociated(peripheral orextrinsic)• Loosely bound tomembrane• Enzymes andstructural proteins

Other Phospholipid Behaviors inH 2 O:• Phospholipid bilayer• Micelle– Role in digestion andabsorption of fats in GItract• Liposome– Larger, bilayer, hollowcenter with aqueous coreClinical relevance?

Movement across MembraneMembrane permeability varies fordifferent molecules & cell typesTwo movement categories:• Passive anddepends on??• Active

Diffusion Process (Passive)•Uses energy of concentrationgradient•Net movement until state ofequilibrium reached (no moreconc. gradient)•Direct correlation to temperature(why?)•Indirect correlation to moleculesize•Slower with increasing distance•Lipophilic molecules can difusethrough the phospholipid bilayerFig 5-5

Distance – Time RelationshipTime for diffusion to progress to givendistance ~ to distance squareddiffusion over 100 m takes 5 sec.diffusion over 200 m takes ??diffusion over 400 m takes ??diffusion over 800 m takes ??Diffusion effective only over short distances!

Fick’s law of Diffusion (p 135)rate ofdiffusion =surface area x conc. gradientmembrane resistance x membrane thicknessdepends onsize and lipid-solubility of molecule andcomposition of lipid bilayer

Fig 5-7Membrane Proteins

Protein-Mediated Transport• More selective– Active or Passive• Membrane Proteins– Structural– Enzymes– Receptors– Transporters (allows Specificity,Competition, Saturation p 145)• Channel• Gated

TransportersCell Membrane Regulates Exchange withEnvironmentMany molecules use transporters to crosscell membrane. Why? Examples ?Two categories of transporter proteins1. Channel proteins (rapid but not asselective – for small molecules only, e.g.,water and ions)2. Carrier proteins (slower but veryselective – also works for large molecules)

1. Channel Proteins• For small moleculessuch as ??• Aquaporin; plus > 100ion channels• Selectivity based on size& charge of molecule• All have gate region– Open– Gated

Open Channels vs. Gated Channels= poresHave gates, but gates areopen most of the time.Also referred to as “leakchannels”.Gates closed most of the timeChemically gated channels(controlled by messenger molecule orligand)Voltage gated channels(controlled by electrical state of cell)Mechanically gatedchannels (controlled by physicalstate of cell: temp.; stretching of cellmembrane etc.)

2. Carrier Proteins• Never form direct connectionbetween ECF and ICF – 2 gates!• Bind molecules and changeconformation• Used for small organicmolecules (such as?)• Ions may use channels orcarriers• Rel. slow (1,000 to 1 Mio / sec)

Symport• Molecules are carriedin same direction• Examples: Glucoseand Na +Antiport• Molecules are carriedin opposite direction• Examples: Na + /K +pumpCotransport

Facilitated Diffusion (as a formof carrier mediated transport)Some characteristics same as simplediffusionbut also:• specificity• competition• saturationFigs 5-18/20

Active Transport• Movement from low conc.to high conc.• ATP needed• Creates state ofdisequilibrium• 1 o (direct) active transport– ATPases or “pumps” (uniportand antiport)– examples?• 2 o (indirect) activetransport– Symport and antiport

1 o (Direct) Active Transport• ATP energy directly fuels transport• Most important example: Na + /K + pump = sodiumpotassiumATPase (uses up to 30% of cell’s ATP)Fig 5-16• Establishes Na+ conc.gradient E pot. canbe harnessed forother cell functionsICF: high [K + ],low [Na + ]ECF: high[Na + ], low [K + ]

Mechanism of the Na + /K + -ATPasestartFig 5-17

2 o (Indirect) Active Transport• Indirect ATP use: usesE pot. stored inconcentration gradient (ofNa + and K + )• Coupling of E kin of onemolecule with movementof another molecule• Example: Na + / Glucosesymporter– other examples• 2 mechanisms for Glucosetransport

Body Fluid CompartmentsIC fluidEC fluidExchangemuch moreselective;Why ?Interstitial fluidplasmaRelatively free exchangeFig 5-13

Body Fluid Compartments:CriticalThinkingQuestionECFICFWhat properties should a molecule have to be used as marker forone of the fluid compartments?Do total H 2 O; total EC and plasma. Then, how do you figure outICF and interstitial fluid?

Vesicular TransportMovement of macromolecules across cellmembrane:1. Phagocytosis (specialized cells only)2. Endocytosis– Pinocytosis– Receptor mediated endocytosis– (Caveolae) Potocytosis3. Exocytosis

1. Phagocytosis• Requires energy• Cell engulfs particle into vesicle viapseudopodia formation• E.g.: some WBCs engulf bacteria• Vesicles formed are much larger than thoseformed by endocytosis• Phagosome fuses with lysosomes ? (see Fig.5-23)

2. Endocytosis• Requires energy• No pseudopodia - Membrane surface indents• Smaller vesicles• Nonselective: Pinocytosis for fluids & dissolvedsubstances• Selective:– Receptor Mediated Endocytosis via clathrin-coated pits -Example: LDL cholesterol and FamilialHypercholesterolemia– Podocytosis via caveolae Fig 5-24

3. ExocytosisIntracellular vesicle fuses with membrane Requires energy (ATP) and Ca 2+Examples: large lipophobic molecule secretion;receptor insertion; waste removal

Movement through Epithelia:Transepithelial transportUses combination of active and passive transportMolecule mustcross twophospholipidbilayersApical and basolateral cell membranes have differentproteins:Na + - glucose transporter on apical membraneNa + /K + -ATPase only on basolateral membrane Fig 5-26

Transcytosis• Endocytosis vesicular transport exocytosis• Moves large proteins intact• Examples:– Absorption of maternalantibodies frombreast milk– Movement of proteinsacross capillaryendothelium

Distribution of Solutes in BodyDepends on• selective permeability of cell membrane• transport mechanisms availableWater is in osmotic equilibrium (freemovement across membranes)Ions and most solutes are in chemicaldisequilibrium (e.g., Na-K ATPase Pump)Electrical disequilibrium between ECF andICFFig 5-33

OsmosisCompare to Fig. 5-29Movement of water down itsconcentration gradient.OsmoticpressureOpposesmovementof wateracrossmembraneWater moves freely in body until osmoticequilibrium is reached

Molarity vs. OsmolarityIn chemistry:• Mole / L• Avogadro’s # / LIn PhysiologyImportant is not # ofmolecules / L but# of particles / L: osmol/Lor OsMWhy?Osmolarity takes into accountdissociation (solubility) of moleculesin solutionOsmolality = OsM/Kg of sol’n

Convert Molarity to OsmolarityOsmolarity = # of particles / L of solution• 1 M glucose = 1 OsM glucose• 1 M NaCl = 2 OsM NaCl• 1 M MgCl 2 = 3 OsM MgCl 2• Osmolarity of human body ~ 300 mOsM• Compare isosmotic, hyperosmotic, hyposmotic (p156)

Tonicity• Physiological term describing howcell volume changes if cell placed inthe solution• Always comparative. Has no units.– Isotonic sol’n = No change in cell– Hypertonic sol’n = cell shrinks– Hypotonic = cell expands• Depends not just on osmolarity buton nature of solutes and permeabilityof membrane

Penetrating vs. NonpenetratingSolutes• Penetrating solute: can enter cell(glucose, urea)• Nonpenetrating solutes: cannot entercell (sucrose, NaCl*)• Determine relative conc. ofnonpenetrating solutes in solution andin cell to determine tonicity.– Water will move to dilute nonpenetrating solutes– Penetrating solutes will distribute to equilibriumFig 5-30

IV Fluid Therapy2 different purposes:– Get fluid into dehydrated cells or– Keep fluid in extra-cellular compartment

Electrical Disequilibrium andResting Membrane Potential(pp.156-163) will be covered at thebeginning of Ch 8

Which of the following is a way for solutesin a aqueous solution to move from anarea of high solute concentration to anarea of low solute concentration?A. Facilitated diffusionB. OsmosisC. Active transportD. A and BE. None of these

Which of the following defines theterm specificity?A. movement of molecules by the use ofvesiclesB. the energy required to movemoleculesC. a group of carrier proteins operatingat their maximum rateD. carrier transport of a group of closelyrelated moleculesE. none of these

Water will always move from___________ situations to _______situations.A. Hyperosmotic, hyposmoticB. Hyposmotic, hyperosmoticC. Hyposmotic, isosmoticD. Hyperosmotic, isosmotic

Which of the following pairs of molecularcharacteristics favors diffusion throughthe cell membrane?A. Large, polarB. Large, non-polarC. Small, polarD. Small, non-polar

Which of the following is a way for solutesin a aqueous solution to move from anarea of high solute concentration to anarea of low solute concentration?A. Facilitated diffusionB. OsmosisC. Active transportD. A and BE. None of these