Plasma Membrane Structure and Function

The plasma membrane separates the internal environment of the cell from its surroundings.

The plasma membrane is a phospholipid bilayer with embedded proteins.

The plasma membrane has a fluid consistency and a mosaic pattern of embedded proteins.

Fluid-mosaic model of membrane structure

Cells live in fluid environments, with water inside and outside the cell.

Hydrophilic polar heads of the phospholipid molecules lie on the outward-facing surfaces of the plasma membrane.

Hydrophobic nonpolar tails extend to the interior of the plasma membrane.

When phospholipids have carbohydrate chains attached, they are called glycolipids.

When proteins have carbohydrate chains attached, they are called glycoproteins.

Carbohydrate chains occur only on the exterior surface of the plasma membrane.

The outside and inside surfaces of the plasma membrane are not identical.

Lipids are non-polar (hydrophobic) compounds, soluble in organic solvents.

Most membrane lipids are amphipathic, having a non-polar end and a polar end.

Fatty acids consist of a hydrocarbon chain with a carboxylic acid at one end.
Non-polar polar

A 16-C fatty acid: CH3(CH2)14-COO-

A 16-C fatty acid with one cis double bond between C atoms 9-10 may be represented as 16:1 cis 9.

 4 2 3 1

O C O

Double bonds in fatty acids usually have the cis configuration. Most naturally occurring fatty acids have an even number of carbon atoms.
fatty acid with a cis-9 double bond
18:1

Some fatty acids and their common names: 14:0 myristic acid; 16:0 palmitic acid; 18:0 stearic acid; cis9 oleic acid 18:2 cis9,12 linoleic acid 18:3 cis9,12,15 -linonenic acid 20:4 cis5,8,11,14 arachidonic acid 20:5 cis5,8,11,14,1 eicosapentaenoic acid !an ome"a-3#

 4 2 3 1

O C O

fatty acid with a cis-9 double bond

$here is free rotation a%o&t C-C %onds in the fatty acid hydrocar%on, e'cept (here there is a do&%le %ond)

*ach cis do&%le %ond ca&ses a kink in the chain)

+otation a%o&t other C-C %onds (o&ld permit a more linear str&ct&re than sho(n, %&t there (o&ld %e a ,in,)

-lycerophospholipids
CH2OH

OH

Glycerophospholipids !phospho"lycerides#, are common constit&ents of cell&lar mem%ranes) $hey ha.e a glycerol %ac,%one) /ydro'yls at C1 0 C2 are esterified glycerol to fatty acids)

CH2OH

Formation of an ester:
O R'OH + HO-C-R" O R'-O-C-R'' + H2O

An ester forms when a hydroxyl reacts with a carboxylic acid, with loss of H2O.

1hosphatidate
O O R1 H2C O O P O C O CH O H2C O C R2

phosphatidate

2n phosphatidate: fatty acids are esterified to hydro'yls on C1 0 C2 the C3 hydro'yl is esterified to Pi)

O O C H2C O O P O X O CH O H2C O C R2

R1

glycerophospholipid

2n most glycerophospholipids !phospho"lycerides#, Pi is in t&rn esterified to OH of a polar head group !X#: e)"), serine, choline, ethanolamine, glycerol, or inositol)

$he 2 fatty acids tend to %e non-identical) $hey may differ in len"th and3or the presence3a%sence of do&%le %onds)

O O C H2C O H OH H OH H H OH OH H H OH O P O O CH O H2C O C R2

R1

phosphatidylinositol

Phosphatidylinositol, (ith inositol as polar head "ro&p, is one "lycerophospholipid)

2n addition to %ein" a mem%rane lipid, phosphatidylinositol has roles in cell si"nalin")

O H2C O H2C O O P O CH2 CH2 CH O CH3 + N CH3 CH3 O C R2

R1

phosphatidylcholine

Phosphatidylcholine, (ith choline as polar head "ro&p, is another "lycerophospholipid)

2t is a common mem%rane lipid)

O O R1 H2C O C O CH O P O O X H2C O C R2

*ach "lycerophospholipid incl&des a polar re"ion: glycerol, carbonyl O of fatty acids, Pi, 0 the polar head "ro&p !X#
glycerophospholipid
polar "kink" due to double bond non-polar

non-polar hydrocar%on tails of fatty acids ! 1, 2#)

Aside from phospholipid, cholesterol is another lipid in animal plasma membranes; related steroids are found in plants.

Cholesterol strengthens the plasma membrane.

Cholesterol, an

HO

important constituent of cell membranes, has a rigid ring system and a short branched hydrocarbon tail. 4holesterol is lar"ely hydrophobic)
Cholesterol

5&t it has one polar "ro&p, a hydro!yl, ma,in" it amphipathic)

HO

Cholesterol

Cholesterol in membrane

Cholesterol inserts into %ilayer mem%ranes (ith its hydro'yl "ro&p oriented to(ard the a6&eo&s phase 0 its hydropho%ic rin" system ad7acent to fatty acid chains of phospholipids)

$he OH "ro&p of cholesterol forms hydro"en %onds (ith polar phospholipid head "ro&ps)

Interaction with the relatively rigid cholesterol decreases the mobility of hydrocarbon tails of phospholipids.

Cholesterol in membrane

But the presence of cholesterol in a phospholipid membrane interferes with close packing of fatty acid tails in the crystalline state, and thus inhibits transition to the crystal state.

Phospholipid membranes with a high concentration of cholesterol have a fluidity intermediate between the liquid crystal and crystal states.

"#o strategies %y (hich phase chan"es of mem%rane lipids are a.oided:

Cholesterol is a%&ndant in mem%ranes, s&ch as plasma mem%ranes, that incl&de many lipids (ith lon"-chain sat&rated fatty acids)

2n the a%sence of cholesterol, s&ch mem%ranes (o&ld crystalli8e at physiolo"ical temperat&res)

$he inner mitochondrial mem%rane lac,s cholesterol, %&t incl&des many phospholipids (hose fatty acids ha.e one or more double bonds, (hich lo#er the melting point to %elo( physiolo"ical temperat&re)

Lateral mobility of a lipid, within the plane of a membrane, is depicted at right .

Lateral Mobility

High speed tracking of indi.id&al lipid molec&les has sho(n that lateral mo$ements are constrained (ithin small mem%rane domains) Hopping from one domain to another occ&rs less fre6&ently than rapid mo.ements (ithin a domain) $he apparent constraints on lateral mo.ements of lipids !and proteins# has %een attri%&ted to inte"ral mem%rane proteins, anchored to the cytos,eleton, f&nctionin" as a picket fence)

Flip-flop of lipids (from one half of a bilayer to the other) is normally very Flip Flop slow. 9lip-flop (o&ld re6&ire the polar head-"ro&p of a lipid to tra.erse the hydropho%ic core of the mem%rane)

$he t#o leaflets of a %ilayer mem%rane tend to differ in their lipid composition)

%lippases cataly8e flip-flop in mem%ranes (here lipid synthesis occ&rs)

Some mem%ranes contain en8ymes that acti$ely transport partic&lar lipids from one monolayer to the other)

peripheral lipid anchor

Membrane proteins may be classified as: peripheral integral having a lipid anchor
lipid bilayer integral

Membrane Proteins

Peripheral proteins are on the mem%rane surface) $hey are (ater-sol&%le, (ith mostly hydrophilic s&rfaces) :ften peripheral proteins can %e dislod"ed %y conditions that disr&pt ionic & H-bond interactions, e)"), e'traction (ith sol&tions containin" hi"h concentrations of salts, chan"e of p/, and3or chelators that %ind di.alent cations)

peripheral lipid anchor

lipid bilayer

integral

Membrane Proteins

'ntegral proteins ha.e domains that e'tend into the hydrocar%on core of the mem%rane)

:ften they span the %ilayer)

2ntramem%rane domains ha.e lar"ely hydrophobic surfaces, that interact (ith mem%rane lipids)

membrane detergent solubilization polar non-polar Protein with bound detergent

Amphipathic detergents are required for solubilization of integral proteins from membranes.

Hydrophobic domains of deter"ents s&%stit&te for lipids, coatin" hydropho%ic s&rfaces of inte"ral proteins) Polar domains of deter"ents interact (ith (ater) 2f deter"ents are remo.ed, p&rified inte"ral proteins tend to aggregate 0 come o&t of sol&tion) $heir hydropho%ic s&rfaces associate to minimi8e contact (ith (ater)

membrane

Cytochrome oxidase dimer

(PDB file 1OCC)

Cytochrome o!idase is an inte"ral protein (hose intramem%rane domains are mainly transmem%rane -helices)

;em%rane transport

How molecules cross the plasma membrane

The Permeability of the Plasma Membrane

The plasma membrane is differentially permeable.

Macromolecules cannot pass through because of size, and tiny charged molecules do not pass through the nonpolar interior of the membrane.

Small, uncharged molecules pass through the membrane, following their concentration gradient.

Movement of materials across a membrane may be passive or active.

Passive transport does not use chemical energy; diffusion and facilitated transport are both passive.

Active transport requires chemical energy and usually a carrier protein.

Exocytosis and endocytosis transport macromolecules across plasma membranes using vesicle formation, which requires energy.

Diffusion

Diffusion is the passive movement of molecules from a higher to a lower concentration until equilibrium is reached.

Gases move through plasma membranes by diffusion.

Diffusion

$he net mo.ement of a substance (molecules) do(n a concentration gradient from an area of high concentration to an area of lo# concentration) +O energy is e'pended)

passi$e transport*

facilitated diffusion* type of passi$e transport (hich &ses transport proteins,

Transport Proteins

"ransports molecules or ions across %iolo"ical mem%ranes 3 types of transport proteins* 1) uniport

2) symport

3) antiport

Proteins that act as carriers are too lar"e to mo.e across the mem%rane)

$hey are transmem%rane proteins, (ith fi!ed topology)

<n e'ample is the G-."1 "l&cose carrier, in plasma mem%ranes of .ario&s cells, incl&din" erythrocytes)

-=>$1 is a lar"e inte"ral protein, predicted .ia hydropathy plots to incl&de 12 transmem%rane -helices)

conformation change

conformation change

Carrier-mediated solute transport

Carrier proteins cycle bet#een conformations in (hich a sol&te %indin" site is accessi%le on one side of the mem%rane or the other)

$here may %e an intermediate conformation in (hich a %o&nd s&%strate is inaccessi%le to either a6&eo&s phase)

?ith carrier proteins, there is ne$er an open channel all the (ay thro&"h the mem%rane)

conformation change

conformation change

Carrier-mediated solute transport

$he transport rate mediated %y carriers is faster than in the a%sence of a catalyst, %&t slo#er than #ith channels)

< carrier transports one or fe# solute molecules per conformational cycle, (hereas a sin"le channel openin" e.ent may allo( fl&' of many tho&sands of ions)

Carriers e'hi%it /ichaelis-/enten kinetics)

Uniport A A B A

Symport

Antiport

4lasses of carrier proteins

.niport !facilitated diff&sion# carriers mediate transport of a sin"le sol&te)

<n e'ample is the G-."1 "l&cose carrier)

Uniport Transport Protein

4arries a single solute across the mem%rane)

extracellular fluid

intracellular fluid

Symport Transport Protein

"ranslocate 2 different solutes sim&ltaneo&sly in same direction)

extracellular fluid

intracellular fluid

Antiport Transport Protein

0!changes 2 solutes %y transportin" them in opposite directions)

extracellular fluid

intracellular fluid

Osmosis

$he mo.ement of #ater across selecti$ely permeable membranes)

$he #ater mo.es from a high concentration to lo# concentration)

Hypertonic

< solution (ith a greater solute concentration compared to another solution)

3% NaCl
97% H2O

solution 5% NaCl 95% H2O

Red Blood Cell

Hypotonic

< solution (ith a lo#er solute concentration compared to another solution)

3% Na
97% H2O

Red Blood Cell

solution 1% Na 99% H2O

Isotonic

< solution (ith an e1ual solute concentration compared to another solution)

3% Na 97% H2O

solution 3% Na 97% H2O

Red Blood Cell

Movement of H2O

?ater (ill 23-43567 diff&ses do(n a concentration "radient from a H5PO"O+'C solution to a H5P0 "O+'C solution)

23-4356 0/0/80 7 H5PO"O+'C

H5P0 "O+'C

Animal Cells

3nimal cells placed into a hypotonic solution (ill H0/O-56'6 (09P-O:0), 3nimal cells placed into a hypertonic solution (ill C 0+3"0 (6H ';0-),

Hemolysis Crenation Red Blood Cells

Transport by Carrier Proteins

Some biologically useful molecules pass through the plasma membrane because of channel proteins and carrier proteins that span the membrane.

Carrier proteins are specific and combine with only a certain type of molecule.

Facilitated transport and active transport both require carrier proteins.

Facilitated transport

During facilitated transport, substances pass through a carrier protein following their concentration gradients.

Facilitated transport does not require energy.

The carrier protein for glucose has two conformations and switches back and forth between the two, carrying glucose across the membrane.

Facilitated diffusion of glucose

Active Transport

$he mo$ement of molecules !small or lar"e# across the plasma membrane in (hich energy (3"P) is re6&ired)

0!amples*

1, 2, 3,

6odium (+a) - Potassium (<) Pump 0!ocytosis 0ndocytosis

Active transport

During active transport, ions or molecules are moved across the membrane against the concentration gradient from an area of lower to higher concentration.

Energy in the form of ATP is required for the carrier protein to combine with the transported molecule.

Active transport

Sodium-Potassium Pump

$he mechanism that &ses energy (acti$e transport) released from splitting 3"P to transport 6odium (+a=) o&t of and Potassium (<=) into cells,
intracellular fluid

extracellular fluid

K+

K+ Na+

Na+

Carrier proteins involved in active transport are called pumps.

The sodium-potassium pump is active in all animal cells, and moves sodium ions to the outside of the cell and potassium ions to the inside.

The sodium-potassium pump carrier protein exists in two conformations; one that moves sodium to the inside, and the other that moves potassium out of the cell.

The sodium-potassium pump