Chapter 7Chapter 7

Membrane Structure and FunctionMembrane Structure and Function

Figure 7.1 The plasma membrane Figure 7.1 The plasma membrane

Plasma membrane:Plasma membrane: --- the boundary that separates the living cell from its --- the boundary that separates the living cell from its

nonliving surroundings.nonliving surroundings.

--- 8 nm thick--- 8 nm thick

--- * --- * Selective permeabilitySelective permeability

The staple ingredients of membranes:

--- Lipids and proteins; (carbohydrates are also important)

Phospholipids:

Membrane Membrane

structurestructure

--- major components of cell membranes.

““ AmphipathicAmphipathic” molecule:” molecule:

--- has both a--- has both a hydrophilic hydrophilic region and a region and a hydrophobichydrophobic region. region.

How are phospholipids and proteins arranged in How are phospholipids and proteins arranged in

the membranes of cells ?the membranes of cells ?

Fluid mosaic model

In In 19151915, , Charles OvertonCharles Overton hypothesized that hypothesized that membranes are membranes are

made of lipids made of lipids (membranes of RBC were isolated, analyzed (membranes of RBC were isolated, analyzed

and found to be composed of lipids and proteins).and found to be composed of lipids and proteins).

In In 19171917, , Irving LangmuirIrving Langmuir made artificial membranes by made artificial membranes by

adding phospholipids dissolved in benzene to water.adding phospholipids dissolved in benzene to water.

In In 19251925, , E. Gorter and F. GrendelE. Gorter and F. Grendel reasoned that cell reasoned that cell

membranes must actually be membranes must actually be phospholipid bilayers, two phospholipid bilayers, two

molecules thickmolecules thick

Membrane models have evolved to fit new data

Figure 7.2 Phospholipid bilayer (cross section)Figure 7.2 Phospholipid bilayer (cross section)

Hydrophilichead

Hydrophobictail

WATER

WATER

If we assume that a phospholipid bilayer is the main

fabric of the membrane, where do we place the

proteins ?In 1935, Hugh Davson and Jam Danielli: sandwich model

(a phospholipid bilayer between two layers of globular protein)

~ this model was widely accepted until about 1970.

Two problemsTwo problems with the model: with the model:

1. The generalization that all membranes of the cell are 1. The generalization that all membranes of the cell are

identical was challenged. identical was challenged.

--- Not all membranes look alike through the EM.--- Not all membranes look alike through the EM.

plasma membrane: 7-8 nm thickplasma membrane: 7-8 nm thick

inner membrane of mitochondria: 6 nm thickinner membrane of mitochondria: 6 nm thick

--- protein level; the kinds of phospholipids and other --- protein level; the kinds of phospholipids and other

lipidlipid

(Membranes with different functions differ (Membranes with different functions differ

in chemical composition and structure)in chemical composition and structure)

2. The placement of the proteins. 2. The placement of the proteins.

--- membrane proteins are not very --- membrane proteins are not very

soluble in water. (soluble in water. (amphipathicamphipathic))

In 1972, S. J. Singer and G. Nicolson:

~ place the proteins in a location compatible with their

amphipathic character.

Fluid mosaic model

Figure 7.3 The fluid mosaic model for membranesFigure 7.3 The fluid mosaic model for membranes

Phospholipidbilayer

Hydrophobic region of protein

Hydrophobic region of protein

Figure 7.4 Research Method Freeze-FractureFigure 7.4 Research Method Freeze-Fracture

APPLICATION A cell membrane can be split into its two layers, revealing the ultrastructure of the membrane’s interior.

TECHNIQUE A cell is frozen and fractured with a knife. The fracture plane often follows the hydrophobic interior of a membrane, splitting the phospholipid bilayer into two separated layers.

Extracellularlayer

Proteins

Cytoplasmic layer

Knife

Plasmamembrane

These SEMs show membrane proteins (the “bumps”) in the two layers, demonstrating that proteins are embedded in the phospholipid bilayer.

RESUTS

Extracellular layer Cytoplasmic layer

The fluidity of membranesThe fluidity of membranes

--- are not static sheets of molecules locked rigidly in place.--- are not static sheets of molecules locked rigidly in place.

--- a membrane is held together primarily by --- a membrane is held together primarily by hydrophobic hydrophobic

interactions.interactions.Lipid

* Lateral movement (frequent)

~ rapid, 107/sec, ~ 2 m/sec.

* Flip-flop (rare)

Protein• larger, move more slowly• Some membrane proteins move in a highly directed manner (driven along cytoskeletal fibers by motor protein)• Many are immobile (attach to cytoskeleton)

Figure 7.6 Inquiry Do membrane proteins move?Figure 7.6 Inquiry Do membrane proteins move?

EXPERIMENT Researchers labeled the plasma membrane proteins of a mouse cell and a human cell with two different markers and fused the cells. Using a microscope, they observed the markers on the hybrid cell.

Membrane proteins

Mouse cell

Human cellHybrid cell

Mixedproteinsafter1 hour

RESULTS

CONCLUSION The mixing of the mouse and human membrane proteins indicates that at least some membrane proteins move sideways within the plane of the plasma membrane.

+

Membranes remain fluid as temperature decreases:Membranes remain fluid as temperature decreases:

~ until finally the phospholipids ~ until finally the phospholipids

settle into a closely packed settle into a closely packed

arrangement and the membranearrangement and the membrane

solidifies.solidifies.

The temperature at which a The temperature at which a

membrane solidifies membrane solidifies depends on depends on

the types of lipids it is made ofthe types of lipids it is made of..

* * Unsaturated hydrocarbon tailsUnsaturated hydrocarbon tails

(( 不飽和脂肪酸不飽和脂肪酸 ))

Kinks Kinks – where double bonds are located; keep the molecules – where double bonds are located; keep the molecules

from from

packing together, enhancing membrane fluidity.packing together, enhancing membrane fluidity.

The membranes remain fluid to a lower The membranes remain fluid to a lower temperature if it is rich in phospholipids with temperature if it is rich in phospholipids with unsaturated hydrocarbon tails.unsaturated hydrocarbon tails.

Cholesterol (膽固醇 ):

~ has different effects on membrane fluidity at different

temperatures.

* At warm temperatures (37oC):

--- cholesterol makes the membrane less fluid by restraining the

movement of phospholipid.

* Cholesterol also hinders the close packing of

phospholipids,

it lowers the temperature required for the membrane to solidify.

Figure 7.5 The fluidity of membranesFigure 7.5 The fluidity of membranes

Lateral movement(~107 times per second)

Flip-flop(~ once per month)

Fluid Viscous

Unsaturated hydrocarbontails with kinks

Saturated hydro-Carbon tails

(a) Movement of phospholipids

(b) Membrane fluidity

(c) Cholesterol within the animal cell membrane

Cholesterol

Cholesterol :

As a “temperature buffer”

for the membrane

The lipid composition of The lipid composition of

cell membrane can cell membrane can

change as an change as an

adjustment to changing adjustment to changing

temperature.temperature.

Ex, winter wheatEx, winter wheat

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Figure 7.7 The detailed structure of an animal cell’s plasma membrane, in cross section

Glycoprotein

Carbohydrate

Microfilamentsof cytoskeleton Cholesterol Peripheral

protein Integralprotein

CYTOPLASMIC SIDEOF MEMBRANE

EXTRACELLULAR

SIDE OFMEMBRANE

Glycolipid

Fibers ofextracellularmatrix (ECM)

Figure 7.8 The structure of a transmembrane proteinFigure 7.8 The structure of a transmembrane protein

EXTRACELLULARSIDEN-terminus

C-terminus

Helix

CYTOPLASMICSIDE

Consist of Consist of nonpolar amino nonpolar amino acidsacids

Attach to cytoskeleton.Attach to cytoskeleton.

Attach to ECM.Attach to ECM.

Six major functions exhibited by proteins of the plasma membrane:Six major functions exhibited by proteins of the plasma membrane:

Membrane is a functional mosaicMembrane is a functional mosaic

The role of membrane carbohydrates in cell-cell recognitionThe role of membrane carbohydrates in cell-cell recognition

Cell-cell recognition--- a cell’s ability to distinguish one type of neighboring cell from

another.

Important in

* sorting the cells into tissue and

organs in an animal embryo.

* rejection of foreign cells** glycoprotein** glycolipid

The carbohydrates on the external side of the plasma

membrane vary from species to species, among individuals of

the same species, and even from one cell type to another in a

single individual.

--- Function as markers Ex. Human blood type.

carbohydratecarbohydrate

-- branched oligosaccharides < 15 sugar units-- covalent bond (共價鍵結 )

Synthesis and sidedness of membrane --- membranes

have distinct inside and outside faces:

* The two lipid layers may differ in specific lipid composition,

and

each protein has directional

orientation in the membrane.

* Carbohydrates:

--- restricted to the exterior

surface.The The asymmetrical distributionasymmetrical distribution of of

proteins, lipids, and their proteins, lipids, and their

associated carbohydrates in the associated carbohydrates in the

plasma membrane is determined plasma membrane is determined

as the membrane is being built as the membrane is being built

by the by the ER and Golgi apparatus.ER and Golgi apparatus.

ER

Transmembraneglycoproteins

Secretoryprotein

Glycolipid

Golgiapparatus

Vesicle

Transmembraneglycoprotein

Membrane glycolipid

Plasma membrane:Cytoplasmic face

Extracellular face

Secretedprotein

4

2

3

1

Concept 7.2: Membrane structure results in selective Concept 7.2: Membrane structure results in selective

permeabilitypermeability A cell must exchange materials with its surroundings, a A cell must exchange materials with its surroundings, a

process controlled by the plasma membraneprocess controlled by the plasma membrane

The Permeability of the Lipid BilayerThe Permeability of the Lipid Bilayer

Hydrophobic molecules (nonpolar)Hydrophobic molecules (nonpolar) Are lipid soluble and can pass through the membrane Are lipid soluble and can pass through the membrane

rapidly (ex. hydrocarbons, COrapidly (ex. hydrocarbons, CO22, O, O22))

Polar moleculesPolar molecules Do not cross the membrane rapidlyDo not cross the membrane rapidly

The lipid bilayer is only part of the story of a membrane’s selective permeabiligyThe lipid bilayer is only part of the story of a membrane’s selective permeabiligy

Proteins built into the membrane play key roles in regulating transport !!Proteins built into the membrane play key roles in regulating transport !!

Transport proteinTransport protein

(channel protein)(channel protein)

Ex. HEx. H22O: aquaporinsO: aquaporins

Specific molecularsSpecific moleculars Selective permeability

Lipid bilayer

Specific transport proteins

What determines the direction of traffic across a membrane ?What determines the direction of traffic across a membrane ?

Two modes of membrane traffic:Two modes of membrane traffic:

Passive transportPassive transport and and active transportactive transport..

Transport proteinsTransport proteins Allow passage of hydrophilic substances across the Allow passage of hydrophilic substances across the

membranemembrane

Concept 7.3: Passive transport is diffusion of a substance Concept 7.3: Passive transport is diffusion of a substance across a membrane with no energy investmentacross a membrane with no energy investment

DiffusionDiffusion Is the tendency for molecules of any substance to Is the tendency for molecules of any substance to

spread out evenly into the available spacespread out evenly into the available space

Figure 7.11 A

Diffusion of one solute. The membrane has pores large enough for molecules of dye to pass through. Random movement of dye molecules will cause some to pass through the pores; this will happen more often on the side with more molecules. The dye diffuses from where it is more concentrated to where it is less concentrated (called diffusing down a concentration gradient). This leads to a dynamic equilibrium: The solute molecules continue to cross the membrane, but at equal rates in both directions.

(a) Molecules of dyeMolecules of dye Membrane (cross section)Membrane (cross section)

Net diffusion Net diffusion Equilibrium

Equal concentrationEqual concentration

Dynamic equilibriumDynamic equilibrium

Substances diffuse down their Substances diffuse down their concentration gradientconcentration gradient, the difference in , the difference in

concentration of a substance from one area to anotherconcentration of a substance from one area to another

Figure 7.11 B

Diffusion of two solutes. Solutions of two different dyes are separated by a membrane that is permeable to both. Each dye diffuses down its own concen-tration gradient. There will be a net diffusion of the purple dye toward the left, even though the total soluteconcentration was initially greater onthe left side.

(b)

Net diffusion

Net diffusion

Net diffusion

Net diffusion Equilibrium

Equilibrium

No work must be done !! Diffusion is a No work must be done !! Diffusion is a spontaneous processspontaneous process !! !!

Effects of Osmosis on Water BalanceEffects of Osmosis on Water Balance

OsmosisOsmosis Is the movement of water across a semi-permeable Is the movement of water across a semi-permeable

membranemembrane Is affected by the Is affected by the

concentration gradient concentration gradient

of of dissolved substancesdissolved substances

Figure 7.12

Higherconcentrationof sugar

Same concentrationof sugar

Selectivelypermeable mem-brane: sugar mole-cules cannot passthrough pores, butwater molecules can

More free watermolecules (higher

concentration)

Water moleculescluster around sugar molecules

Fewer free watermolecules (lowerconcentration)

Water moves from an area of higher free water concentration to an area of lower free water concentration

Osmosis

Lowerconcentrationof solute (sugar)

Water Balance of Cells Without WallsWater Balance of Cells Without Walls

TonicityTonicity Is the ability of a solution to cause a cell to gain or lose waterIs the ability of a solution to cause a cell to gain or lose water Has a great impact on cells without wallsHas a great impact on cells without walls

If a solution isIf a solution is isotonicisotonic:: The concentration of solutes is the same as it is inside the The concentration of solutes is the same as it is inside the

cellcell There will be no net movement of waterThere will be no net movement of water

If a solution is If a solution is hypertonichypertonic:: The concentration of solutes is greater than it is inside the The concentration of solutes is greater than it is inside the

cellcell The cell will lose waterThe cell will lose water If a solution is If a solution is hypotonichypotonic:: The concentration of solutes is less than it is inside the The concentration of solutes is less than it is inside the

cellcell The cell will gain waterThe cell will gain water

Water balance in cells without wallsWater balance in cells without walls

Figure 7.13

Hypotonic solution Isotonic solution Hypertonic solution

Animal cell. Ananimal cell fares bestin an isotonic environ-ment unless it hasspecial adaptations tooffset the osmoticuptake or loss ofwater.

(a)

H2O H2O H2O H2O

LysedLysed NormalNormal ShriveledShriveled

Animals and other organisms without rigid cell walls Animals and other organisms without rigid cell walls

living in hypertonic or hypotonic environmentsliving in hypertonic or hypotonic environments

Must have special adaptations for osmoregulationMust have special adaptations for osmoregulation

Osmoregulation:Osmoregulation:

--- the control of water balance.--- the control of water balance.

1. Less permeable plasma membrane1. Less permeable plasma membrane

2. Contractile vacuole2. Contractile vacuolehypotonichypotonic

Water Balance of Cells with WallsWater Balance of Cells with Walls

Cell walls: Help maintain water balanceCell walls: Help maintain water balance

* If a plant cell is * If a plant cell is turgidturgid It is in a hypotonic environmentIt is in a hypotonic environment It is very firm, a healthy state in most plantsIt is very firm, a healthy state in most plants

* If a plant cell is * If a plant cell is flaccidflaccid It is in an isotonic environmentIt is in an isotonic environment

Plant cell. Plant cells are turgid (firm) and generally healthiest ina hypotonic environ-ment, where theuptake of water iseventually balancedby the elastic wallpushing back on thecell.

(b)

H2OH2OH2OH2O

Turgid (normal)Turgid (normal) FlaccidFlaccid PlasmolyzedPlasmolyzed

Facilitated Diffusion: Facilitated Diffusion: Passive Transport Aided by ProteinsPassive Transport Aided by Proteins

In facilitated diffusionIn facilitated diffusion Transport proteins Transport proteins speedspeed the movement of molecules the movement of molecules

across the plasma membraneacross the plasma membrane

Channel proteinsChannel proteins Provide corridors that allow a specific molecule or ion to Provide corridors that allow a specific molecule or ion to

cross the membrane (cross the membrane (* aquaporins: water channel proteins)

Figure 7.15

EXTRACELLULAR FLUID

Channel proteinSolute

CYTOPLASM

A channel protein (purple) has a channel through which A channel protein (purple) has a channel through which water molecules or a specific solute can pass.water molecules or a specific solute can pass.

(a)(a)

* Ion channel* Ion channel ::

function as function as gated gated

channelschannels

- a stimulus causes - a stimulus causes

them them

to open or close.to open or close.

electrical or chemical !electrical or chemical !

Carrier proteinsCarrier proteins Undergo a subtle change in shape that translocates the Undergo a subtle change in shape that translocates the

solute-binding site across the membranesolute-binding site across the membrane Ex. Cystinuria Ex. Cystinuria (absence of a protein that transports cysteine)(absence of a protein that transports cysteine)

Figure 7.15

Carrier proteinSolute

A carrier protein alternates between two conformations, moving a solute across the membrane as the shape of the protein changes. The protein can transport the solute in either direction, with the net movement being down the concentration gradient of the solute.

(b)

Concept 7.4: Active transport uses energy to Concept 7.4: Active transport uses energy to move solutes against their gradientsmove solutes against their gradients

The Need for The Need for EnergyEnergy in Active Transport in Active Transport

Active transportActive transport Moves substances Moves substances against their concentration gradientagainst their concentration gradient Requires energy, usually in the form of Requires energy, usually in the form of ATPATP

Active transport is the pumping of solutes against their Active transport is the pumping of solutes against their

gradientsgradients

--- the major factor in the ability of a cell to maintain internal --- the major factor in the ability of a cell to maintain internal

concentrations concentrations

of small molecules that differ from concentrations in its environment.of small molecules that differ from concentrations in its environment.

K+

Na+

Sodium-potassium Sodium-potassium pumppump

Review: Passive and active transport comparedReview: Passive and active transport compared

Figure 7.17

Passive transport. Substances diffuse spontaneously down their concentration gradients, crossing a membrane with no expenditure of energy by the cell. The rate of diffusion can be greatly increased by transport proteins in the membrane.

Active transport. Some transport proteins act as pumps, moving substances across a membrane against their concentration gradients. Energy for this work is usually supplied by ATP.

Diffusion. Hydrophobicmolecules and (at a slow rate) very small uncharged polar molecules can diffuse through the lipid bilayer.

Facilitated diffusion. Many hydrophilic substances diffuse through membranes with the assistance of transport proteins,either channel or carrier proteins.

ATP

All cells have All cells have voltagesvoltages across their plasma membrane across their plasma membrane

((電壓電壓 ))

cytoplasmcytoplasm --- “ --- “ negativenegative” charge” charge

extracellularextracellular --- “ --- “ positivepositive” charge” charge

The voltage across a membrane, called a The voltage across a membrane, called a membrane membrane

potential.potential.

(~-50 to -200 millivolts)(~-50 to -200 millivolts)

~ favors the passive transport of cations into the cell and anions ~ favors the passive transport of cations into the cell and anions

out of out of

the cell.the cell.

Unequal distribution of anions and cations on opposite sides of the membrane

TwoTwo forces drive the diffusion of ions across a membrane: forces drive the diffusion of ions across a membrane:

--- a --- a chemicalchemical force (the ion’s concentration gradient) force (the ion’s concentration gradient)

--- an --- an electricalelectrical force (the effect of the membrane potential on the force (the effect of the membrane potential on the

ion’s movement)ion’s movement)

Electrochemical gradient

An ion does not simply diffuse down its concentration gradient, but diffuses down its electrochemical gradient.

Maintenance of Membrane PotentialMaintenance of Membrane Potential by by Ion PumpsIon Pumps

Membrane potential: Membrane potential: is the voltage difference across a membraneis the voltage difference across a membrane

An electrochemical gradientAn electrochemical gradient Is caused by the concentration electrical gradient of ions Is caused by the concentration electrical gradient of ions

across a membraneacross a membrane

* An* An electrogenic pump electrogenic pump

+

H+

H+

H+

H+

H+

H+ Proton pump

ATP

CYTOPLASM

+

+

+

+–

–

–

–

–

+

EXTRACELLULARFLUID

~ Is a transport protein ~ Is a transport protein

that generates the that generates the

voltagevoltage across a across a

membranemembrane

Ex. Ex. Sodium-potassium pumpSodium-potassium pump

Proton pump (plants)Proton pump (plants)

Cotransport: Cotransport: Coupled TransportCoupled Transport by a Membrane by a Membrane ProteinProtein

Proton pump

Sucrose-H+

cotransporter

Diffusionof H+

Sucrose

ATP H+

H+

H+

H+

H+

H+

H+

+

+

+

+

+

+–

–

–

–

–

–

CotransportCotransport~ A single ATP-powered pump that transports a specific ~ A single ATP-powered pump that transports a specific

solute solute

can indirectly drive the active transport of several other can indirectly drive the active transport of several other

solutes in a mechanism called cotransport.solutes in a mechanism called cotransport.The protein can The protein can translocate sucrose into translocate sucrose into the cell against a the cell against a concentration gradient, concentration gradient, but but only if the sucrose only if the sucrose molecule travels in the molecule travels in the company of a hydrogen company of a hydrogen ionion..

sucrose-Hsucrose-H++ pump pump

Figure 7.19Figure 7.19

Concept 7.5: Bulk transport across the plasma Concept 7.5: Bulk transport across the plasma membrane occurs by membrane occurs by exocytosisexocytosis and and endocytosisendocytosis

Large proteinsLarge proteins Cross the membrane by different mechanismsCross the membrane by different mechanisms

In In exocytosisexocytosis Transport vesicles migrate to the plasma membrane, Transport vesicles migrate to the plasma membrane,

fuse with it, and release their contentsfuse with it, and release their contents

In In endocytosisendocytosis The cell takes in macromolecules by forming new The cell takes in macromolecules by forming new

vesicles from the plasma membranevesicles from the plasma membrane

* * Water and small solutes: Water and small solutes: directly passdirectly pass through the lipid bilayer of through the lipid bilayer of

the the

plasma membrane or by plasma membrane or by transport transport

proteinsproteins. .

* Large molecules (ex, proteins and polysaccharides): * Large molecules (ex, proteins and polysaccharides): involving involving

vesiclesvesicles

Exocytosis and endocytosis transport large

molecules.

* Many secretory cells use exocytosis to export their

products. ex. Pancrease : insulin

neuron : release neurotransmitter.

* Endocytosis:

3 type --- phagocytosis (cellular eating)

pinocytosis (cellular drinking): unspecific

receptor-mediated endocytosis: specific

(ligand --- receptor)Cholesterol travels in the blood in particles called low-density lipoproteins (LDLs), complexes of lipids and proteins

bind to LDL receptors on membranes and then enter the cells by endocytosis.

HypercholesterolemiaHypercholesterolemia atherosclerosisatherosclerosis

EXTRACELLULARFLUID

PseudopodiumCYTOPLASM

“Food” or other particle

Foodvacuole

1 µm

Pseudopodiumof amoeba

Bacterium

Food vacuole

An amoeba engulfing a bacterium viaphagocytosis (TEM).

PINOCYTOSISPINOCYTOSIS

Pinocytosis vesiclesforming (arrows) ina cell lining a smallblood vessel (TEM).

0.5 µm

In pinocytosis, the cell “gulps” droplets of extracellular fluid into tinyvesicles. It is not the fluiditself that is needed by the cell, but the molecules dissolved in the droplet. Because any and all included solutes are taken into the cell, pinocytosisis nonspecific in the substances it transports.

Plasmamembrane

Vesicle

In phagocytosis, a cellengulfs a particle by Wrapping pseudopodia around it and packaging it within a membrane-enclosed sac large enough to be classified as a vacuole. The particle is digested after the vacuole fuses with a lysosome containing hydrolytic enzymes.

Three types of endocytosisThree types of endocytosis

Figure 7.20

PHAGOCYTOSISPHAGOCYTOSIS

0.25 µm

RECEPTOR-MEDIATED ENDOCYTOSISRECEPTOR-MEDIATED ENDOCYTOSIS

Receptor

Ligand

Coat protein

Coatedpit

Coatedvesicle

A coated pitand a coatedvesicle formedduringreceptor-mediatedendocytosis(TEMs).

Plasmamembrane

Coatprotein

Receptor-mediated endocytosis enables the cell to acquire bulk quantities of specific substances, even though those substances may not be very concentrated in the extracellular fluid. Embedded in the membrane are proteins with specific receptor sites exposed to the extracellular fluid. The receptor proteins are usually already clustered in regions of the membrane called coated pits, which are lined on their cytoplasmic side by a fuzzy layer of coat proteins. Extracellular substances (ligands) bind to these receptors. When binding occurs, the coated pit forms a vesicle containing the ligand molecules. Notice that there are relatively more bound molecules (purple) inside the vesicle, other molecules (green) are also present. After this ingested material is liberated from the vesicle, the receptors are recycled to the plasma membrane by the same vesicle.