biological membranes

structure of biological membranes

Lipids and proteins (with carbohydrates attached)

lipid structures in aqueous solution

In aqueous solutions amphiphilic (polar) lipids try to minimise contact between hydrophobic lipid chains and water molecules.

spontaneous formation of various structures

polar head groups are oriented towards the water, hydrophobic tails are oriented towards each other 

micelle

globular aggregates formed from the sats of fatty acids 

lipid bilayer

preferred structure of phospholipids

liposome

solvent-filled vesicle bounded by lipid bilayer

Properties of the lipid bilayer

• Very stable

• Models of biological membranes

• Vehicles for drug delivery

• Absorbed by many cells by fusion with plasma membrane

lipid bilayers - polarity

Hydrophilic interaction between polar head groups maximised

Hydrophobic interaction facilitate association of hydrocarbon chain in interior of the bilayer

Bilayers have a polar surface and a non-polar core

Non-polar core is a permeability barrier - ions and other polar molecules cannot easily cross it

biological membranes

lipid bilayers are the base structure for biological membranes

boundaries of cells and intracellular organelles 

Membranes are composed of lipids and proteins, both can have carbohydrates attached

lipid mobility in membranes

Lipids in bilayer membranes are not static (fluid-like properties)

Lateral diffusion and rotation are rapid -> lipid bilayers can be viewed as two-dimensional fluid

Transverse diffusion (flip-flop movements) are rare, require passage of polar heads through hydrophobic core

lipid asymmetry

ATP-dependent transport of phospholipids from one side to the other by phospholipid translocase - non-equilibrium distribution

Different lipid composition of inner and outer leaflet of bilayer

lipid bilayer phase transition 

Motion (fluidity) of lipids in bilayer depends on temperature

Lipids in bilayer exist in different states

Transition between states takes place at transition temperature or melting temperature Tm.

pure phospholipid bilayers

transition occurs over narrow temperature range

native membrane

broader temperature range of  transition, depends on proteins and lipid composition

intermediate state between gel and liquid

this is essential for optimal functioning of membrane

how is membrane fluidity regulated 

transition temperature of lipid bilayers 

• Increases with fatty acid side chain length

• Decreases with unsaturation

• Lipid composition

regulation of membrane fluidity

In eukaryotes cholesterol is the key regulator of membrane fluidity.

Cholesterol affects fluidity in 2 ways:

1. Cholesterol rigid steroid ring system restricts the mobility f non-polar tails, thus makes the membrane feel less fluid

2. Cholesterol prevents tight packaging of fatty acid chains, thus prevents transition to gel state

Maintenance of intermediate state over a range of conditions

Bacteria do not contain sterols in their membranes, but regulate membrane fluidity by varying the ratio of unsaturated to saturated fatty acids

• E-coli ratio changes from 0.38 to 1.6 as growth temperature is lowered from 40 to 30 degrees Celsius

membrane proteins

Proteins are major components of biological membranes

Lipid-protein ratio vary in different membranes

• Inner mitochondria membrane is 76% protein (chemical reactions)

• Myelin membrane is only 18% protein (lipid rich to insulate nerve axons)

• Plasma membrane is ~50% protein

Proteins carry out most membrane processes

• Chemical reactions

• Mediate flow of nutrients and wate

• Signalling

freeze fracture experiments

Cells are frozen in liquid nitrogen

Frozen cells are fractured using a knife

The fracture occurs preferentially between the lipid bilayer of the plasma membrane

fluid mosaic model

• Membranes are dynamic structures

• Phospholipid bilayer is a fluid matrix that functions as a two-dimensional solvent for proteins (supports lateral diffusion)

• Proteins are icebergs floating in a two-dimensional lipid sea

• Membranes are more mosaic than fluid

experimental test

Mouse protein labelled green, human protein labelled red

Immediately after fusion the mouse and human proteins are segregated

After a time the green and red markers are fully intermixed

FRAP: fluorescence recovery after photobleaching

Membrane component of an immobilised cell is labelled with a fluorescent marker (fluorophore) - A

An intense laser light pulse bleaches the fluorescence in a small area - B

Fluorescence is restored after some time due to lateral diffusion - C

mobility of lipids and proteins 

Most lipids can freely diffuse with some exceptions - lipid rafts

Lateral diffusion of proteins can be

• Unrestricted (only depended on size/molecular weight)

• Restricted: anchored to intracellular proteins, such as spectrin (cytoskeletal protein)

• Restricted: association with lipid rafts

lipid rafts

Distribution of lipids not uniform - membrane microdomains

Enriched in sphingolipids, cholesterol and certain proteins (closely packed)

Segregation, more ordered arrangement, slightly thicker

Insoluble in non-ionic detergents

function of lipid rafts

• Cluster proteins, seems to be important in certain complex signalling

• Viruses such as influenza tend to localise to lipid rafts and may be the site where they enter the cells