Biological Membranes

• plasma membrane all cells• encloses contents of entire cell

membrane-bound organelles of eukaryotic cells:• nuclear ‘envelope’• double membranes of mitochondria and chloroplasts

• endoplasmic reticulum• Golgi apparatus• lysosomes / vacuoles• transport vesicles• et al.

• membrane lipids form closed, double-layered sheets• no free edges

• within cell, membranes form extensive interconnected networks

• lipid bilayers will ‘self assemble’ in aqueous solution

• membranes are deformable• important for cell fusion, budding, locomotion

Biological Membranes

source of figure: Alberts Fig 10-5

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flat sheet of phospholipid bilayer with edges exposed to water:energetically unfavorable / unstable

sealed compartment:energetically favorable / stable

source of figure: Alberts Fig 10-5

Doxil (liposomal doxorubicin)

http://www.doxil.com/

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Membrane Functions• compartmentalization

• create separate environments for different activities

• scaffold for biochemical activities

• provide a selectively permeable barrier• prevent unrestricted exchange of molecules

• transport solutes• exchange of molecules across the membrane

• respond to external signals - signal transduction• signals travelling from a distance or from nearby cells

• energy transduction - conversion of one form of energy into another

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Components of Biological Membranesamphipathic lipids arranged in a bilayer• form backbone - prevent random movement of water soluble

molecules in / out

proteins• perform most of the specific functions of a particular

membrane or patch of membrane

carbohydrates• attached to proteins and lipids in a non-random way

relative amts of components variable, depending on:• type of organism (prokaryote vs animal vs plant)• type of cell within organism (muscle, liver, sperm, egg, …)• type of membrane within cell (plasma membrane, Golgi, ER)• different patches or ‘domains’ within a particular membrane

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Phospholipid: Phosphatidyl Choline

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Membrane Phospholipids

fatty acid chains

glycerolphosphate

polar head group

phosphatidyl choline (PC)

phosphatidyl serine (PS)

phosphatidyl ethanolamine (PE)

phosphatidyl inositol (PI)

Asymmetry of Membrane LipidsExtracellular

Cytosolic

e.g. human red blood cell:• PC and SM (sphingomyelin) mostly outer leaflet; • PS, PE, PI mostly inner

• the appearance of PS in outer ‘leaflet’ of membrane usually indicates that cell is going to die

cholesterol

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Human RBCs as ‘Model Organism’ for Plasma Membrane• best understood plasma membrane!

• cells are inexpensive and available in large numbers

• already present in single cell suspension

• simple - no nucleus, ER, lysosomes, mitochondria• very pure preps of plasma membranes

• purified intact plasma membranes can be prepared by producing red blood cell ‘ghosts’

Fig 6.26

“Fluid Mosaic” Model of Membranes

old view of membranes, as static ‘sandwiches’ (Fig 6.18) has been replaced

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“Fluid Mosaic” Model of Membranes

• phospholipids are constantly moving• spinning in place; travelling laterally within leaflet

• some phospholipids are ‘flipped’ to the opposite leaflet during membrane synthesis but they rarely ‘flop’ back

• even proteins cruise slowly through the membrane!

Factors affecting Membrane Stiffness or ‘Fluidity’

• mostly related to alignment of phospholipid tails:

• degree of saturation of FAs

• presence of cholesterol

• temperature

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Lipid Composition and Membrane Fluidity

• fatty acid tails – saturated versus unsaturated

Fig 6.9 Fig 6.10

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Cholesterol and Membrane Fluidity

• under physiological conditions, cholesterol makes membrane stiffer – less fluid• cholesterol can make up to 50% of plasma membrane

lipid in some animal cells

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Temperature and Membrane Fluidity

• at and above ‘room temperature’ phospholipids in membranes are fluid, and move freely

• as temperature drops, fluidity (and permeability) decreases

• at very low temps, hydrophobic tails pack together and membrane ‘gels’ (solidifies)

above transition temp below transition temp

transition temp = temp at which membrane ‘gels’

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Regulation of Membrane Fluidity• fluid state must be maintained for normal cell function

strategies for maintaining membrane fluidity:• change composition of membranes

• alter phospholipids• desaturate fatty acids (to deal with cold)

• eg cold water vs warm water fish• change length of FA chains (yeast, bacteria)

• adjust amounts of cholesterol (animals)

these mechanisms have been demonstrated in:• pond fish dealing with dramatic day / night temp differences• cold-resistant plants• extremophile bacteria living in hot springs• winter wheat preparing for autumn ↑ polyunsaturated FAs• sperm reduce their cholesterol just before fertilization …

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Membrane Proteins

• peripheral proteins can be attached to phospholipids or other proteins

• asymmetrically distributed inside versus outside cell

extracellular

cytosolic

peripheralmembraneprotein

integral protein(trans-membrane)

peripheralmembraneprotein

Non-polar regions lock proteins into membranes.

phospholipids

polar areasof protein

nonpolar areas ofprotein

• penetrate hydrophobic core of membrane• can be single pass, multi-pass, pores

NH2

H+

COOH

H+

Proteins folded into a helices can form channels.

C

N

b-pleated sheets

Proteins folded into pleated sheets can form pores.

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Peripheral Membrane Proteins

• located outside the lipid bilayer• can be extracellular or intracellular• typically function in signal transduction or anchoring cell

Major Functions of Membrane Proteins