Biomembrane

• Biomembranes


  Plays a central role in the structure and function of all cells
• Biomembranes


  • Approximately 5-8 nm(50-80Å) thick
  • Used as cell boundaries and acts a permeability barrier
  • Organize and compartmentalize specific activities within and around the cell
  • Facilitates communication and transportation
  • Energy Storage
• Biomembranes composition


  • All biomembranes have the same basic structure: phospholipid bilayer
  • Except Archeabacteria which have a monolayer that looks and behaves like a bilayer
  • Each phospholipid layer is called a leaflet
  • The specific activities of the membrane is determined by the set of proteins associated with it
  • Proteins account for half of the mass of the membrane
  • Glycolipids and glycoproteins (lipids and proteins with attached carbohydrates)
  • Sterols, example cholesterol (for animal cells) and stigmasterol (generally found in plants)

  
• Lipid composition of a membrane

  • Phospholipid
  • Sterols
  • Glycolipids

  
• Phospholipid


  • Major component of most biomembranes
  • Amphipathic properties
  • Example: phosphatidylcholine (lecithin), phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine and sphingomyelin
  • Highly dynamic
  • Lateral mobility
  • Flipping between leaflets
  • Responsible for membrane permeability

  
• Phospholipid structure


  • Built from lipid and steroid derivatives
  • Glycerol backbone
  • Connected to fatty acid chains by ester bonds (one or more fatty acid)
  • Phosphate group (head)
  • A functional/hydrophilic group – gives the phospholipid its name

  
• Major phospholipids in mammalian plasma membranes

  • Phosphatidylcholine
  • Phosphatidylserine
  • Phosphatidylethanolamine
  • Sphingomyelin

  
• Fatty acid


  • Forms the tail of the phospholipid structure
  • Strongly non-polar
  • Usually, even number of carbons
  • The presence of double bonds in unsaturated fatty acids creates bends and "loosen up membrane packing"

  
• Sterols


  • Another class of membrane lipids
  • All have four hydrocarbon rings
  • Cholesterol is a steroid (lipid soluble)
  • Very abundant and necessary in animal cells, as it accounts for 20% of the lipids found
  • Present in both leaflets of bilayer
  • Amphipathic
  • Membrane fluidity "buffer"
  • Synthesized in the membrane of the endoplasmic reticulum

  
• Cholesterol


  • Can be called a "temperature buffer" because at higher temperature (like body temp.) it makes the phospholipid less fluid by restraining their movements
  • At lower temperatures cholesterol hinders the close packing of the phospholipids so it lowers the temperature required for membranes to solidify
  • Plants contain sterols like stigmasterol and sitosterol in their cell membrane
  • In bacterial cell membranes, sterols are absent
• Glycolipids


  • Have a carbohydrate group covalently attached to the lipid part of the molecule
  • For these structure either glycerol or sphingosine and has sugar in place of phosphate head
  • Least common of the membrane lipids (~2%)
  • Always found on the outer leaflet of the membrane
  • Involved in cell identity (e.g., blood group antigens)

  
• Integral (intrinsic) or Transmembrane Proteins


  • Span the lipid bilayer either in a single or multiple pass
  • Penetrates the hydrophobic core
  • Only removed by disrupting the bilayer
  • Types: Transmembrane proteins, Covalently tethered integral proteins
  • Function: Transport, Enzymatic, Signal Transduction (Receptors), Cell-cell recognition (Communication), Intercellular joining, Attachment to cytoskeleton and extracellular matrix (Adhesion)
  • Synthesized in rough endoplasmic reticulum

  
• Peripheral (extrinsic) Proteins


  • Loosely associated with membrane surface
  • Does not interact with hydrophobic core of bilayer
  • Associated with membrane by lipid anchors, interaction with the bilayer, or contact with integral proteins
  • Located on both extracellular and intracellular sides of the membrane
  • Synthesis: Cytoplasmic (inner) side - cytoplasm, Extracellular (outer) side - made in ER and exocytosed

  
• Function of membrane proteins

  • Transport nutrients
  • Allows the passage of water
  • Selective transport of molecules by keeping out unwanted molecules
  • Maintains the ionic composition of the cell
  • Receptor site for extracellular environment
  • Expression of cell identity
  • Physical and functional connection with other cells or extracellular matrix
• Membrane carbohydrates


  • Third major component of the plasma membrane
  • Found on the outer leaflet
  • Mainly linked to proteins (forming glycoproteins) or lipids (forming glycolipids)
  • Some membrane carbohydrates are part of proteoglycans that insert their amino acid chain among the lipid fatty acids
  • The polysaccharide chains are composed of 2-60 monosaccharide units that can be either straight or branched and coat the surface of all eukaryotic cells

  
• Types of membrane carbohydrates

  • Glycoproteins - proteins attached to one or more oligosaccharides, involved in cell recognition and surface antigenicity
  • Glycolipids - carbohydrates covalently linked to membrane lipids, involved in maintaining cell stability and facilitating cellular recognition
  • Proteoglycans - long polysaccharide chains linked covalently to a protein core, found mainly outside the cell as part of the extracellular matrix, some have protein core that extends across the lipid bilayer or is attached by a GPI anchor

  
• In the membrane structure diagram, the structure labelled D is the Phospholipid bilayer, B is the Glycolipid, and F is the Peripheral protein

  
• Membrane dynamics


  • Asymmetry
  • Fluidity
  • Lateral Mobility
• Asymmetry of the membrane

  • The inner and outer leaflets of the membrane have different compositions of lipids and proteins
  • Asymmetrical distribution of all integral and membrane bound proteins
  • Glycolipids are exclusively located on the exoplasmic leaflet

  
• Fluidity of the membrane

  • Maintaining the fluidity bilayer is essential for normal cell growth and reproduction
  • Dependent on temperature and lipid composition
  • Hydrophobic interior has a low viscosity and a fluid-like rather than gel-like consistency
• How lipid composition affects fluidity

  • All cell membranes contain a mixture of different fatty acyl chains, which are fluid at the temperature the cell is grown
  • Decrease fluidity (movement) due to interactions between hydrophobic tails
  • Short (unsaturated) tails have fewer interactions, stable at low temperatures
  • Cholesterol is major determinant in membrane fluidity, widens the range of the Tm, effect dependent on lipid composition, prevents interaction, restrict tail movement

  
• Lateral mobility


  • Mobility (diffusion) of a given membrane components depends on lipid composition (tails, cholesterol), the size of the molecule, its interactions with other molecules, and temperature
  • Interaction between temperature and membrane, temperature "melts" the membrane

  
• Membrane transport


  • Exchange of material by cell with its surrounding is controlled by the plasma membrane
  • Facilitates nutrients in and waste out the cell
  • Hydrophobic (nonpolar) molecules such as hydrocarbons, can dissolve in the lipid bilayer
  • Most biologically important solutes require protein carriers to cross the cell membrane
  • This process is done by either passive or active transport
• Selective permeability


  • Cell membranes are selectively permeable
  • Some solutes cross the membrane freely, some cross with assistance, and others do not cross at all
• Permeability of the bilayer

  • Only lipid-soluble molecules and some small molecules can freely pass through the lipid bilayer
  • Ions and large polar molecules cannot pass through the lipid bilayer
  • Whether a molecule can pass through the membrane depends on its size and its electrical nature

  
• Molecules permeable to the bilayer

  • Small hydrophobic molecules: lipid soluble molecules
  • Nonpolar molecules: O2; CO2
  • Small uncharged polar molecules: H2O

  
• Molecules impermeable to the bilayer

  • Ions: Na+; K+ Cl-
  • Large polar molecules: sugars, proteins

  
• Passive transport


  • Involves the movement of molecules across the cell membrane without the requirement of energy expenditure (ATP)
  • Goes from a higher concentration to a lower concentration
  • There three types: simple diffusion, facilitated diffusion, osmosis
• Diffusion


  • The movement of any substance from a higher concentration to a lower concentration until a balance is reached
  • After equilibrium is attained the molecules keep moving but the balance remains the same
• Facilitated diffusion


  • Transport aided by integral proteins
  • Spontaneous movement of molecules or ions across a biological membrane through specific transmembrane proteins
  • Channel proteins provide corridors that allow the movement of specific molecules and ions across the membrane
• Osmosis


  • Involves the movement of water across membranes
  • Dependent on the relative concentration of solute molecules in and outside the cell
• Active transport


  • The pumping of molecules against their concentration gradient (A LOW CONCENTRATION to a HIGH CONCENTRATION) with the expenditure of energy (ATP)
  • Sometimes cells requires the uptake of molecules that are scarce in their environment
  • This process uses energy to facilitate the transportation of these materials against its concentration gradient
  • Types: Ion Pump, Cotransport, Endocytosis
• Lipid rafts


  • Small (10-200nm), heterogeneous, highly dynamic, sterol- and sphingolipid-enriched domains that compartmentalize cellular processes
  • Cholesterol and sphingolipid-enriched membrane microdomains or platforms
  • Contains 3-5 times more cholesterol than in the surrounding bilayer
  • Glycosphingolipid levels elevated by 50%
  • More ordered and tightly packed than surrounding bilayer
  • Able to move or "float" freely in the membrane bilayer

  
• Types of lipid rafts

  • Planar lipid rafts (non-caveolar or glycolipid rafts)
  • Caveolae (flask shaped inward folding of the plasma membrane, contains caveolin proteins)
• Why do lipid rafts need cholesterol?

  • Cholesterol is the dynamic "glue" that holds the raft together
  • Interacts preferentially but not exclusively with sphingolipids due to structure and saturation of hydrocarbon chains
  • Ability to pack in between the lipid rafts, thereby serving as molecular spacer and filling voids
  • Up to 25% of cholesterol is found in the brain
  • When removed, most proteins dissociate from the raft structure
• Functions of lipid rafts

  • Serves as the organizing centres for the assembly of signalling molecules
  • Influences membrane fluidity
  • Influences membrane protein interactions (such as protein sorting during endocytosis and exocytosis, cell adhesion and migration)
  • Regulates neurotransmissions and receptor trafficking
  • Involved in Apoptosis
  • Point of entry for a wide range of viruses, bacteria and toxins
  • Site for the formation of both prions and Alzheimer amyloid
  • Contribute to the formation of immune synapses
  • Contains molecule involved in immune response (such as T- and B- cell receptors)
  • Promotes platelet activation