Membrane Structure and Function - 1 - STEM Digital · PDF fileMembrane Structure and Function...

Membrane Structure and Function - 1

The Cell Membrane and Interactions with the EnvironmentAs mentioned earlier, the boundary between any cell and its environment is theplasma membrane. Each cell must interact with its environment in a number ofways. Each cell needs to obtain oxygen and other nutrients (carbohydrates, aminoacids, lipid molecules, salts, etc.) from the environment, maintain water balancewith its surroundings, and remove waste materials from the cell. The plasmamembrane can do its job because it is differentially, or selectively permeable.The membrane permits some materials to enter and leave easily, some with theassistance of membrane molecules, and other substances are prohibited fromentering or leaving.

The plasma membrane has a number of functions:• Serves as the boundary between the cytoplasm of the cell and the external

environment.• Maintains the cell's environment by regulating materials that enter or leave the

cell.• Provides mechanisms for cell-to-cell communication.• Has genetically unique cell recognition markers to provide mechanisms for a cell

to recognize "self" versus "non-self" (foreign materials), important to theimmune system and defense of the organism.

Note that although the plasma membrane forms the boundary of the cell, andsurrounds the cell, many internal structures of eukaryotic cells also have theirown membrane boundaries. Much of what we say about membrane structure andfunction at this time applies to all membranes, not just the plasma membrane.

The Fluid Mosaic Membrane StructureThe typical membrane structure consists of a phospholipid bilayer. Recall thatphospholipids are molecules with both hydrophilic (polar) and hydrophobic (nonpolar) regions (in other words, they are amphipathic). The fatty acid "tails" of thetwo phospholipid layers are oriented towards each other so that the hydrophilic"heads", which contain the phosphate portion, face out to the environment as wellas into the cytoplasm of the cell's interior, where they form hydrogen bonds withsurrounding water molecules.


Because the individual phospholipid molecules are not bonded to each other, amembrane is flexible (or “fluid”) particularly to lateral movement of the fattyacids, important to its functions. The membrane is held together, for the mostpart, by the hydrophobic interactions. The phospholipid molecules are not bondedto each other, so they tend to move along the plane of the membrane. The rate ofmovement can be measured, averaging two micrometers per second.

Phospholipid Movement Unsaturated/Saturated With Cholesterol

The saturation of fatty acids affects the fluidity -- the more saturated, the lessmovement. Cholesterol, found in membranes of animal cells, reduces fluidmovement of the phospholipids at normal temperatures. Membranes will solidify astemperature decreases. The temperature at solidification depends on thesaturation of the fatty acids (just as it does with fats and oils). Solidifiedmembranes do not function well. Research (reported in Nature) showed that braincell membranes of ground squirrels become more solid during hibernation. Proteinsmigrate to more fluid regions of the membrane so they can continue to function. Incaribou, circulation is reduced in the lower legs to prevent excess heat loss duringcold winters. The membranes of the lower legs have more unsaturated fatty acidsthan those of the upper legs to retain more fluidity in reduced temperatures.


Membrane ProteinsInterspersed throughout a membrane’s phospholipid layer are a number ofamphipathic proteins. The orientation of the proteins is such that hydrophobicregions of the proteins are within the fatty acid regions of the phospholipids andhydrophilic regions of the proteins are at the aqueous interfaces of the membrane(interior and exterior). This orientation is important to how the membraneproteins function.

Some proteins are mobile within the membrane (probably moved by motormolecules of the cytoskeleton) and others are fixed in position. The membrane isassociated with a network of supporting cytoskeletal filaments, some of which helpshape the cell and some help anchor proteins in the membrane.

Membranes also contain some carbohydrates (glycoproteins and proteoglycans)and glycolipids on the exterior side. The resultant membrane structure (proteinsscattered throughout the fluid phospholipid layers) resembles a mosaic, hence thename “fluid mosaic membrane”. Proteins in membranes determine how thespecific membrane functions.

Recall that membrane is manufactured in the endoplasmic reticulum. Theorientation of membrane proteins and lipids is determined at the manufacturingsite. Molecules on the inside of the ER and Golgi vesicles become exteriormembrane molecules.

Membrane Protein CategoriesMembrane proteins are divided into two categories, integral and peripheral,depending on their location. That is the easy part. Biologists further identify themembrane proteins by function – and there are many!

Integral (Transmembrane) ProteinsProteins that go through the membrane are called integral or transmembraneproteins. They have hydrophobic (non-polar amino acids with alpha helix coiling)regions within the interior of the membrane and hydrophilic regions at eithermembrane surface.

Peripheral ProteinsPeripheral proteins are attached to the surface of the membrane, often to theexterior hydrophilic regions of the transmembrane proteins. On the interiorsurface, peripheral proteins typically are held in position by the cytoskeleton. Onthe exterior, proteins may attach to the extracellular matrix. For animal cells,these attached proteins help give the membrane strength.


Membrane Protein FunctionsTransport Proteins

Transport Proteins are transmembrane proteins that serve ascarriers for specific substances that need to pass through the membrane byproviding a hydrophilic channel. Transport proteins have binding sites thatattract specific molecules. Most of our ions (Ca++, Na+, Cl-, K+, etc.), along withamino acids, sugars and other small nutrient molecules are moved throughtransport proteins. When a molecule binds to the carrier protein, the proteinchanges shape moving the substance through the membrane. This process mayrequire energy (ATP), and the ATP complex is a part of the transport protein.When ATP is involved with actively moving molecules through the protein channelthe process is called Active Transport.

Enzymatic Proteins

Many enzymes are embedded in membranes, which attractreacting molecules to the membrane surface. The active site of the enzyme willbe oriented in the membrane for the substrate to attach. Enzymes needed formetabolic pathways can be aligned adjacent to each other to act like an assemblyline for the reactions.

Signal Transduction (Receptor) Proteins

Signal transduction proteins have attachment sites for chemicalmessengers, such as hormones. The signal molecule, when it attaches to theprotein, promotes a conformational change that relays the message into the cellto trigger some cell activity. Chemical messaging in cells is the subject of a laterchapter. These proteins are also called receptor proteins.


Recognition Proteins

Glycoproteins (carbohydrate-protein hybrids) serve as surfacereceptors for cell recognition and identification. They are important to theimmune system so that immune system cells can distinguish between one’s owncells and foreign cells. Recognition proteins are also used to guide cellattachments/adhesions in developmental processes.

Cell Adhesion (Intercellular Joining) Proteins.

Some proteins are responsible for the cell junctions such as tightjunctions and gap junctions that permit cells to adhere to each other.

Attachment Proteins

Attachment proteins attach to the cytoskeleton or extracellularmatrix to help maintain cell shape (particularly for animal cells) and fix intoposition some membrane proteins. Some proteins attach to the cytoskeleton onthe interior of the membrane; others attach to the extracellular matrix ofglycoproteins. Collagen is an important glycoprotein of the extracellular matrix.Some attachment proteins, the integrins, attach to both the extracellular matrixand to the cytoskeleton in the interior of the cell, spanning the membrane.


Structure of the Membrane Proteins Relative to FunctionsAnchoring proteins have non-polar α helix regions that fix the protein into thephospholipid bilayers. Polar regions are on either side of the non-polar regions,attracted to the hydrophilic phospholipid regions.

Anchor proteins are also used to attach to the fibrous network of thecytoskeleton to give shape and strength to some cells.

Channel proteins will have non-polar α helix segments traversing the lipidbilayers many times forming a channel through which the target substance canpass. Often a carrier molecule or "pump" will be embedded in the protein matrix.

Pores are formed when non-polar β pleated sheet regions of proteins create"tunnels" in the membrane lipid bilayers.

Anchoring Protein Channel Protein Pore Protein


Moving Materials Through MembranesA significant part of membrane activity involves transporting materials through itin one direction or the other. Mineral ions, water, amino acids, monosaccharidesand other nutrients are constantly passing through membranes. The cellmembrane is selectively, or differentially, permeable. This means that:• Some materials freely pass - the membrane is permeable to such molecules and

whether they are inside or outside of the cell depends on other factors.• Some materials are excluded• Some materials enter or leave the cell only by using energy

For example, small hydrophobic molecules, such as CO2, O2 and small lipids, dissolvein the membrane and pass through readily. Tiny polar molecules, such as H2O andalcohol, can also minimally slip between the phospholipid molecules. Ions and mostnutrient molecules do not move freely through membranes, but are often carriedby the transport protein channels, either with or without the use of energy. Mostlarge molecules are excluded and must be manufactured within the cell, or movedby significant alterations of the membrane itself.

Before we talk about how molecules move through membranes, it is useful to havesome definitions:• Fluid

Any substance that can move or change shape in response to externalforces without breaking apart. Gases and liquids are fluids.

• ConcentrationThe number of molecules of a substance in a given volume

• GradientA physical difference between two regions so that molecules will tend tomove from one of the regions toward the other. Concentration, pressureand electrical charge gradients are common in cells.

In general, the movement of any substance is subject to “physical rules” ofmolecule behavior. All molecules are in motion (their intrinsic kinetic energy whichis called thermal motion). One effect of this motion is that atoms and moleculesmake random collisions with other molecules. However, when the distribution ofmolecules is not equal, and we have a gradient, there is a net movement ofmolecules along the gradient. Many gradients exist between a cell's environmentand the cytoplasm of the cell. These gradients are important in moving materialsthrough membranes, both passively (without the use of energy by the cell) andactively (transport requiring cell energy).

Movement of most substances takes place by simple diffusion, facilitateddiffusion and active transport. We shall discuss all three. Simple andfacilitated diffusion are means of passive transport. Active transport consumesenergy to move substances against a gradient.


Passive TransportMoving things through membranes without the expenditure of cell energy downgradients.

Simple Diffusion• Diffusion is the movement of a substance from where there is more of it along

a concentration gradient to where there is less of it, until molecules are equallydistributed (and the gradient no longer exists), a state of equilibrium. Strictlyspeaking, we say that molecules will move from where there is more freeenergy to where there is less free energy. Equilibrium means that there in nonet movement. Molecules can and will continue to move, but for every forwardmovement there will be a matching reverse movement.

• Diffusion is a means of passive transport, since no additional energy isexpended for the process. Molecules are moving down an energy gradient, sothe movement is spontaneous.

• In terms of cellular activity, diffusion:• Requires no energy• But the cell has no control over diffusion, and the rate of diffusion is

pretty slow and can not cover much distance.• The Rate of Diffusion can be affected by:

• Temperature (Higher temperature, faster molecule movement)• Molecule size (Smaller molecules often move more easily)• Concentration (Initial rate faster with higher concentration)• Gradient of the two regions (Greater the gradient differential, the

more rapid the diffusion (again, initially))


Materials that may move through membranes by passive diffusion include:• H2O (water) (although much moves via facilitated diffusion)• CO2 (carbon dioxide)• O2(oxygen)• Some lipid-soluble molecules (alcohol)

Note: The movement of water through a differentially permeable membrane inresponse to solute concentrations, the phenomenon of osmosis, is aspecial case of diffusion that we shall discuss later.

Facilitated DiffusionMost molecules cannot move freely through the membrane, but can pass throughmembranes with the help of membrane transport proteins, some of whichtemporarily bind to the substance to be moved through the membrane, a processcalled facilitated diffusion. No energy is involved, so it is still a passiveprocess. Transport proteins are specific, and are limited in number in membranes.The rate of movement of materials is dependent on the availability of transportproteins as well as the concentration of the substance to be moved. In addition,transport proteins can be blocked by some molecule (not the target molecule) thatmay be attracted to the binding site, but does not move through it.

There are a number of different ways in which transport proteins work, and theprecise mechanisms of movement are not fully understood.

• Some have binding sites that attract a polar target molecule; as the targetmolecule builds up in concentration it moves through the open hydrophilicprotein channel along its gradient. Channels for specific ions are commonin membranes. Much water movement through membranes also involvesfacilitated diffusion. There are special channel proteins, called aquaporins,that facilitate the movement of water at a rate needed for cell activities.

• Some transport proteins have channels with gates. The gate opens to letthe target molecule pass through when it receives an electrical or chemicalsignal. For example, neurotransmitter chemicals serve as signal moleculesto open the gates for sodium to flow into the nerve cell.

• Facilitated diffusion also occurs with carrier molecules, substances towhich the target molecule to be transported temporarily binds, resulting in aconformational change that moves the target substance through themembrane.

Facilitated Diffusion Models

Membrane Structure and Function - 1 0

Problems can arise when transport proteins are genetically or developmentallynon-functional. Their target substance cannot be transported, and in some cases,serious problems result.

Materials that move through membranes by facilitated diffusion include:• Glucose• Many small ions• Amino acids

Energy-Requiring Transport Across MembranesAll cells need to move some substances through membranes in a direction counterto the gradient, maintain concentrations of molecules that are not at equilibriumwith the external environment by constantly pumping them into or out of the cell,and move substances that are too large or bulky be moved without the use of cellenergy. Cells have a number of ways to move things with the use of energy.

Active TransportSome transport proteins can move substances through the membrane against theconcentration gradient. Active transport typically requires two active sites on thecarrier protein, one to recognize the substance to be carried, and one to releaseATP to provide the energy for the protein carriers or "pumps". Often, ATPtransfers its phosphate to the transport protein, changing the protein’s shape sothat the target substance can be carried across the membrane. Much energy isexpended by the cell to do this! The sodium/potassium pump, which maintains theappropriate Na+/K+ ion balance in typical animal cells, is one such example.

Note that with the Na+/K+ pump, the carrier protein is exchanging sodium andpotassium ions. The change brought about by the phosphorylation of the transportprotein moves sodium; the release of sodium “permits” the binding of potassiumon the other side of the membrane. The release of the phosphate changes theconformation so that the potassium is carried through the membrane andreleased.

In some cases, concentration gradients of ions, typically H+ or Na+ ions, can be usedto provide the energy needed to move something through a membrane. Thismechanism works because the charges on the ions create an electrochemicalgradient that can be measured as a membrane voltage potential. Most cells arenegatively charged relative to their external surroundings.


Electrogenic pumps use both the charge gradient and the concentrationgradient to facilitate movement. Transport proteins that use charged pumps arecalled electrogenic pumps. The sodium-potassium pump is one example. In thehydrogen proton pump ATP is used to pump H+ across a membrane that buildsup both a concentration and a charge on the other side. The hydrogen protonpump is important in generating a positive change in the extracellular fluid of manyplants, bacteria and fungi. ATP synthesis uses H+ pumps.

Electrogenic Pump Cotransport

Coupled TransportElectrogenic pumps are also used in the processes of coupled transport. Thesubstance to be moved is "coupled" to the concentration of a different substancethat is being transported down a gradient in a protein channel after that substance(typically Na+ or H+) has been actively pumped through the membrane to create aforce.

In cotransport, proton pumps actively move H+ through a membrane that createsa gradient on the other side. Transport proteins then facilitate the movement ofthe H+ back through the membrane along its gradient. This H+ gradient is coupledto the movement of some other substance against its gradient in the samedirection on the transport protein through the membrane. The transportprotein has two binding sites on the same side of the membrane: one for the ionand one for the target substance. For example, in plants, while H+ is moving "down"through a transport protein channel, amino acids may be transported "up" alongwith it. The energy gradient of the H+ provides the energy needed to move theamino acids. Loading sucrose into phloem for translocation in plants uses H+

cotransport. Sodium ions are also used in cotransport, in particular to move aminoacids and sugars. One of the most important metabolic processes of life, ATPsynthesis, typically involves cotransport. H+ is actively pumped to one side of amembrane, building up concentration, charge and pH gradients. As theaccumulated H+ move back through a membrane transport protein (the ATPsynthase complex), their force is used to synthesize ATP. This specific process iscalled chemiosmosis, something we shall discuss later.

In countertransport, the substances coupled move in the opposite direction inthe membrane. The target substance to be moves binds to the opposite side ofthe coupled transport protein as the coupling ion whose gradient will provide theforce to move the target substance.


Membrane Interactions with the EnvironmentLarger substances may require changes in membrane shape and the fusion ofmembranes to move things into or out of cells.

ExocytosisMaterials can be exported from the cell by fusing vesicles with the plasmamembrane, a process called exocytosis. Typically, materials for export arepackaged in the Golgi body and the vesicles formed travel along the cytoskeletonuntil they reach the plasma membrane. Once the vesicle membrane and plasmamembrane fuse, the contents of the vesicle are freed from the cell. For example,insulin, made in cells of the pancreas, leaves the cells of the pancreas byexocytosis. New wall material in plants is secreted via exocytosis.

EndocytosisSubstances which enter the cell using membrane modifications move byendocytosis.

There are three methods of moving by membrane modification: Pinocytosis,receptor-mediated endocytosis and phagocytosis.

• PinocytosisMembrane invaginates, substances "fall" in cavity, used for moving fluids into orout of a cell. Whatever molecules were in the fluid will be moved into the cell.


• Receptor-Mediated EndocytosisHighly specific receptor molecules in the membrane attract the substance tobe moved into the cell, creating a membrane depression in that area (a coatedpit). When sufficient molecules have been attracted, the pocket will be pinchedoff forming a coated vesicle in the cytoplasm. Molecules that bind toreceptor sites are called ligands. (It’s a general term that simply meanssomething that attaches to a receptor.) Cholesterol is transferred from LDLsto individual cells via receptor-mediated endocytosis.

PhagocytosisMembrane pseudopodia surround and engulf particulate objects, packaging themin a membrane-bounded vacuole. Phagocytosis is used for solids large objects,such as prey engulfed by Amoeba, and bacteria by white blood cells.


Now to a Complication of water, membranes and diffusion: OsmosisOsmosis is the movement (diffusion) of water across a differentially permeablemembrane in response to solute (dissolved substances) gradients maintained bythe membrane. The "force" to move water through membranes is called osmoticpressure. It is comparable to physical pressure. Osmotic pressure may beresisted by the cell membrane (if it is strong enough) or the cell wall (in organismsthat have cell walls). The wall or membrane exerts a mechanical pressure. Thedifference in the osmotic pressure and the wall or membrane pressure is known aswater potential. Water potential is very important in a number of processes.

For the process of osmosis:• A membrane separates two solutions and the proportion of solutes to water is

unequal on the two sides of the membrane.• A water gradient exists, in part because dissolved substances always lower the

concentration of water in a solution. (Pure water would have the highestconcentration of water – any substance that is added to pure water will“displace” some water molecules, lowering the proportional content of thewater.) Moreover, solutes attract water to their surfaces forming hydrationshells and when the solutes move along their gradient, the attracted watermoves, too, attracting more water.

• The membrane permits water passage.• The membrane is not permeable to the solute(s), which are substances that can

"bind" to water, affecting the free flow of water.• Since osmosis depends of the differences in the concentration of water, the

specific types of solutes do not matter; it's their collective effect on theconcentration of water than counts. Or, it's not so much the number ofmolecules, or volume of molecules, but the proportions of solutes to water.


There are terms that are used to describe the ratio of water to solutes, and theyare always used to describe the comparative proportion of water to solutes onboth sides of the membrane (or inside of and outside of the cell). When usingthese terms we must be careful to define higher and lower relative to location(inside of or outside of the cell, for example).• Hyperosmotic (Hypertonic) When discussing cells, if the external solution

has a higher solute concentration (less water) than the internal solution, it is ahypertonic solution. There is more water (relative to solutes) inside of the cell.Strictly speaking, the solution that has the higher proportion (concentration) ofsolutes is said to be hyperosmotic or hypertonic. Hyperosmotic solutionswill cause water to leave cells by osmosis, and cells may shrink.

• Hypoosmotic (Hypotonic) The external solution (again, speaking of cells)has a lower solute concentration (more water) than the internal solution of thecell. Hypoosmotic solutions will cause water to enter cells byosmosis, causing the cells to swell.

• Isosmotic (Isotonic) Isotonic solutions will have equal proportions ofsolutes to water on both sides of the membrane. Isosmotic solutions areosmotically balanced and there is no net movement of water. Water will movethrough the membrane, but equal amounts of water will be moving in bothdirections.

Human Red Blood Cells

Typical Plant CellHypoosmotic Isosmotic Hyperosmotic

It is important to understand that the solutions do not have to be identical inosmotic activity. You can have completely different solute substances oneither side of the membrane. It's the total proportion of solutes (which bind towater molecules inhibiting their movement) to water that affects osmosis, notthe specific chemicals.


Effects of OsmosisOsmosis has a tremendous impact on living organisms that are continuouslyexposed to a variety of solutes in their extracellular mediums. Cells cannot affordto either lose water or gain excess water. They must maintain an equal proportionof solutes both inside and outside of the cells, a condition called osmoticbalance, to function. The process by which organisms regulate their osmoticbalance is called osmoregulation. Here are some examples:

Hyperosmotic EnvironmentsAn environment which has a higher proportion of solutes than found inside the cellwill cause water to leave the cell. Salt water, for example, is hypertonic to thecells of many organisms. The cells of an organism placed in sea water will losewater and shrivel, a phenomenon called plasmolysis, unless it has specialmechanisms to prevent this. Salt water organisms have a variety of suchmechanisms.• Sharks circulate urea that increases the solute concentration in their

extracellular fluids to approximate that of sea water.• Most marine invertebrates are isotonic to sea water. (They would not survive in

fresh water.)• Many salt water mammals rely on impervious surfaces to prevent water loss.• A hyperosmotic environment for terrestrial organisms is common, for the

substrate and atmosphere often have a lower proportion of water than theinternal cellular environment. Plant cells plasmolyze when placed in ahypertonic environment and lose turgor, causing the plant to "wilt". Thisroutinely happens when their substrate lacks sufficient moisture. Fortunately,adding water to the substrate reverses the osmotic gradient, creating ahypoosmotic environment so that water moves back into cells. Regrettably,after too long a period of time in a plasmolyzed condition a plant enters a stateof permanent wilt, and does not recover. Some call this death.

Plasmolysis in Plants


Hypoosmotic EnvironmentsAn environment which has a lower proportion of solutes than found inside the cellwill cause water to enter the cell. Fresh water, for example, is hypotonic to thecells of all organisms. The extracellular spaces in plants are typically saturatedwith water vapor as water diffuses into roots and is drawn upward through thexylem tissue to be distributed to cells.

Plant cells take advantage of osmotic pressure, using the cell wall and centralplant vacuole. As mentioned earlier, stored substances in the vacuole attractwater, which increases fluid pressure within the vacuole. This hydrostaticpressure, called turgor pressure, forces the cytoplasm against the plasmamembrane and cell wall, balancing the osmotic pressure to move water into thecell. These balanced forces keep the cell rigid, maintaining turgor. Turgorprovides support and strength for herbaceous plants and other plant parts lackingsecondary cell walls.

Animal cells may swell to bursting when placed in fresh water, a hypoosmoticenvironment. Animal cells, therefore, require some method to prevent this andmaintain osmotic balance.• Many fresh water protists have contractile vacuoles, structures which

collect the water which moves into their cell from the environment, andperiodically expel the collected water to the external environment bycontracting the vacuole though a pore, hence the name, contractile vacuole.

Contractile Vacuole in the Paramecium

Full Empty

• Fresh water fishes continuously excrete a very dilute urine to remove excesswater that enters through their gills.

Note: Most terrestrial animals maintain an isosmotic environment by surroundingthe cells with an osmotically balanced extracellular fluid. Animals havesystems to maintain osmotic balance such as the kidney (and otherregulatory structures) of humans.

Even so, most terrestrial organisms are at risk of dehydration. Bodysurfaces typically have protective layers to minimize this risk, and mostorganisms take in water to compensate for water that diffuses (or isexcreted) out of the body.

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