Module 10 - Cell Membranes

Walls and Membranes

BME 111

Why membranes?

Cells are fundamental functional units of lifeCells may cooperate to form an organismBUT cells must maintain own internal order and structure in order to function properly Differs from environment May differ from adjacent cells

Average human has about 10 X 1012 cells200 different kinds of cells

AnimaliaIngest food

BacteriaProkaryotesUnicellularMicroscopic

ArchaeaProkaryoticunicellularmicroscopic

Eukarya

ProtistaUnicellular eukaryotes

Fungidecomposers

PlantaeProduce their own sugars and food

Prokaryotic Cells

First appeared in fossil record about 3.5 billion years agoAbout 1-10 microns in diameterMost prokaryotes are bacteriaNo membrane bound organellesSingle chromosome Some have extra-

chromosomal piece of circular DNA = plasmid

Prokaryotic Cells

Prokaryotes do not have membrane-bound organelles. This means that they have no mitochondria. So, how do they produce ATP from glucose? The electron transport chain and ATP

synthase is embedded in the plasma membrane (phospholipid bilayer).

Electron Transport chainin Prokaryotes

Prokaryotic ATPase

Impact of Prokaryotes

Nutritionally diverse Some are able to harness light energy through

photosynthesis Some use CO2 as carbon source and extract energy from

inorganic substances such as hydrogen sulfide or ammonia Some must consume organic molecules

Not all are pathogenic to animalsMany participate in chemical recycling, e.g., nitrogenBioremediation - use of organisms to

remove pollutants from water, air, or soil Sewage treatment, e.g., sludge breakdown by

anaerobic bacteria Petroleum Mining sites of heavy metals, arsenic,

copper, zincLavender Pit Mine, Bisbee AZ

Eukaryotic Cells - Animals

Several chromosomesMembrane bound organelles Nucleus Mitochondria Endoplasmic

reticulum Rough Smooth

Golgi apparatus Vacuoles

Eukaryotic - Plant Cells

What is unique in a plant cell?

Plant Cell Walls

Outside of plasma membranesComposed of cellulose and pectinsPrevent cells from bursting

About Cell Membranes

1.All cells have a cell membrane

2.Functions: a.Controls what enters

and exits the cell to maintain an internal balance called homeostasis

b.Provides protection and support for the cell

TEM picture of a real cell membrane.

3.Structure of cell membrane

Lipid Bilayer -2 layers of phospholipidsa.Phosphate head is polar (water loving)

b.Fatty acid tails non-polar (water fearing)

c. Proteins embedded in membrane

About Cell Membranes (continued)

Phospholipid

Lipid Bilayer

Plasma membrane is about 50 atoms thick and serves as a selective barrier.

Eukaryotic cells contain many compartments created by intracellular membranes

Lipid Bilayers

Every cell must be surrounded by a “wall” to separate them from environmentPlasma Membrane Lipid bilayer Spontaneously self-

assembles ~4 nm thick

H2C-C-CH2

PO3

C=O O=C OH

Un

charg

ed

Hyd

rop

hobic

Charg

ed

Hydro

ph

ilic

The phospholipids in the cell membrane are amphipathic.

Phosphatidylcholine is the most common type of phospholipid.

Positive

negative

Three kinds of membrane lipids, all amphipathic, include phospholipids, sterols, and glycolipids.

Hydrophilic heads

Hydrophilic molecules interacting with water molecules.

Hydrophobic molecules in water. Water molecules are repelled by hydrophobic molecules bind to each other

forming a cage structure that prevent direct contact with the hydrophobic molecule

Phospholipid bilayer

polarhydrophilicheads

nonpolarhydrophobictails

polarhydrophilicheads

Self-sealing property

“free edges” are quickly eliminated because they are energetically unfavorable - hydrophobic areas are in contact with water.

The lipids will spontaneously seal and will always form a closed compartment.

A small tear will be repaired. A larger tear may lead to the break up of the membrane into separate vesicles.

With water inside and out, the lipid bilayer remains intact, no lipids leave. However, the lipids do move freely within the bilayer. Experiments use liposomes, which form spontaneously.

Due to thermal motions, lipid molecules within a monolayer rotate very rapidly and diffuse rapidly through the fluid membrane. Any drop in temperature decreases the rate of lipid movement, making the lipid bilayer less fluid. This inhibits many functions of the cell’s membranes. All this has been confirmed in whole cells.

• The fluidity of a lipid bilayer depends on its composition.– As temperature and environment changes, the fluidity of

the cell’s membranes must be kept functional.– The closer and more regular the packing of the tails, the

more viscous and less fluid the bilayer will be– The length and degree of saturation with hydrogens

affect their packing• shorter tails can not interact as much - more fluid• one of the two hydrocarbon tails often has a double bond -

unsaturated. This creates a kink - less packing, more fluid.

• In bacterial and yeast cells, both the lengths and the unsaturation is constantly adjusted to maintain the membrane at a relatively constant fluidity.– At higher temperatures the cell makes longer

tailed lipids with fewer double bonds.• In animal cells, membrane fluidity is

modulated by cholesterol, which is absent in plants, yeast and bacteria.

Cholesterol fills in the spaces left by the kinks; stiffens the bilayer and makes it less fluid and less permeable.

Lipid bilayers are impermeable to solutes and ions. Rate of diffusion varies depending on size and solubility properties. This has been demonstrated in synthetic bilayers.

In this way, cells control the passage of molecules across its membranes

Specialized transport proteins transfer specific substrates across the membrane

• Membrane fluidity is important to a cell for many reasons.– 1. Enables membrane proteins to diffuse rapidly and interact

with one another - crucial in cell signaling etc.– 2. Provides a simple means of distributing membrane lipids and

proteins by diffusion from sites of insertion.– 3. Allows membranes to fuse with one another and mix their

molecules– 4. Ensures that membrane molecules are distributed evenly

between daughter cells.• Remember though, cell has control - cytoskeleton and

other interactions can limit the mobility of specific lipids and proteins.

Membrane is a collage of proteins & other molecules embedded in the fluid matrix of the

lipid bilayer

Extracellular fluid

Cholesterol

Cytoplasm

Glycolipid

Transmembraneproteins

Filaments ofcytoskeleton

Peripheralprotein

Glycoprotein

Phospholipids

Plasma Membrane

Unsaturated Fatty acid

CHOLESTEROLCan make membrane

much stiffer, decrease

packing density

Plasma Membrane Proteins

Alpha helix

extracellular

cytoplasmicCh3 fig 33 Lodish

Membrane Proteins

Proteins determine membrane’s specific functions cell membrane & organelle membranes each

have unique collections of proteins

Membrane proteins: peripheral proteins

loosely bound to surface of membrane cell surface identity marker (antigens)

integral proteins penetrate lipid bilayer, usually across whole membrane transmembrane protein transport proteins

channels, permeases (pumps)

Proteins domains anchor molecule

Within membrane nonpolar amino

acids hydrophobic anchors protein

into membrane

On outer surfaces of membrane polar amino acids

hydrophilic extend into

extracellular fluid & into cytosol

Polar areasof protein

Nonpolar areas of protein

Other trans membrane proteins form aqueous pores that allow water-soluble molecules to cross the membrane. These are more complicated, often cross the bilayer a number of times as alpha-helices or as beta-barrels

In these cases alpha-helices contain both hydrophobic and hydrophilic amino acid side chains, with the hydrophobic side chains on one side and hydrophilic on the other side.

Although the alpha-helix is the most common, transmembrane portions of a protein can be beta-barrels (two beta-sheets connected by a disulfide bond. The loop areas often form the active site or binding site.

Beta-barrels are less versatile since the can form only wide channels.

Transmembrane portions are composed largely of amino acids with hydrophobic side chains. However, the peptide back bone (peptide bonds) is hydrophilic. Therefore, a helical structure is the most energetically favorable.

The peptide bonds are hydrogen bonded to each other in the interior while the hydrophobic amino acid side chains contact the lipid chains.

Many Functions of Membrane Proteins

Outside

Plasmamembrane

InsideTransporter Cell surface

receptorEnzymeactivity

Cell surface identity marker

Attachment to thecytoskeleton

Cell adhesion

The lipid bilayer is asymmetrical, with the cytoplasmic side being different from the non-cytoplasmic side. Proteins are embedded with a specific orientation crucial for their function. Phospholipid composition also varies.

Due to thermal motions, lipid molecules within a monolayer rotate very rapidly and diffuse rapidly through the fluid membrane. Any drop in temperature decreases the rate of lipid movement, making the lipid bilayer less fluid. This inhibits many functions of the cell’s membranes. All this has been confirmed in whole cells.

New phospholipid molecules are synthesized in the ER by membrane-bound enzymes which use substrates (fatty acids) available only on one side of the bilayer.

Flipases transfer specific phospholipid molecules selectively so that different types become concentrated in the two halves. One sided insertion and selective flippases create an asymmetrical membrane

In eukaryotic cells nearly all new membrane synthesis occurs in the ER. The new membrane is exported to the Golgi apparatus for modification and export. Carbohydrate chains are added in the Golgi - glycolipids. The enzymes that add sugar groups to lipids are confined to the Golgi apparatus and sugars are added only to the non-cytoplasmic side. No flippases exist for glycolipids. Forms a protective coat on most animal cells.

Intracellular signal transduction

Most of the proteins in the plasma membrane have short chains of sugars (oligosaccharides) linked to them - glycoproteins. Others have longer polysaccharide chains - proteoglycans. All the glycoproteins, proteoglycans, and glycolipids are found on the noncytosolic side of the lipid membrane. They form a sugar coating called the glycocalyx.

Glycocalyx helps to protect the cell surface from mechanical and chemical damage, absorb water and give the cell a slimy surface to help cells squeeze through narrow spaces and prevent them from sticking to each other or the walls of blood vessels.

The lipid bilayer is a two-dimensional fluid. Many lipids and proteins move freely within the plane. This is demonstrated by staining mouse cells with rhodamine and human cells with fluorescein. These two cells are then fused. Within 30 minutes the proteins from the mouse and human cells have diffused and are intermixed.

However, lipids and proteins do not all float freely in the membrane. The cell controls the movement of many proteins. Cells have ways of confining particular plasma membrane proteins to localized areas, creating membrane domains which are functionally specialized.

Proteins are moved together when signaled by receptors like adhesion molecules.

Tethered to the cell cortex

Bound by the extracellular matrix

Held by proteins on another cell

Stopped by diffusion barriers.

In epithelial cells that line the gut, uptake of nutrients from the gut is confined to the apical surface while proteins involved in the transport of solutes out into the tissues and bloodstream is confined to the basal and lateral surfaces. This asymmetric distribution is maintained by a barrier formed by tight junctions - seals between adjacent cells.