Biological Membranes

• Biological Membranes


  Dynamic structures in which proteins float in a sea of lipids
• Plasma Membrane


  • Protective barrier 7.5-10 nm thick that separates living cells from the surroundings
  • Controls movement of nutrients, ions, proteins etc in and out of cell
  • Determines cell identity and function
  • Facilitates cell communication (signal transduction)
• Components of Plasma Membrane

  • Membrane lipids
  • Membrane proteins
  • Membrane carbohydrates
• Membrane Lipids


  Amphipathic molecules containing both hydrophilic and hydrophobic moieties
• Major Membrane Lipids


  • Phospholipids
  • Glycolipids
  • Cholesterol
• Phospholipids


  Most abundant membrane lipids, consisting of a glycerol or sphingosine backbone, fatty acids, phosphate and an alcohol
• Glycolipids


  Sugar-containing lipids derived from sphingosine, with one or more sugars/carbohydrates attached
• Cholesterol


  Steroid molecule that constitutes up to 50% of membrane lipids in animal cells, absent in prokaryotes
• Bilayer Formation


  1. Phospholipids spontaneously form bilayers in aqueous solutions due to amphipathic nature

  2. Hydrophobic tails interact, forming a hydrophobic interior barrier

  3. Hydrophilic head groups interact with aqueous medium on each side

  4. Bilayers are stabilised by hydrophobic interactions, van der Waals forces, electrostatic and hydrogen bonding
• Lipid Vesicles (Liposomes)


  Aqueous compartments enclosed by a lipid bilayer, used to study membrane permeability or deliver chemicals to cells
• Lipid bilayers


  • Stabilised by electrostatic and hydrogen-bonding attractions between the polar head groups and water molecules
  • Held together by many reinforcing, noncovalent interactions (predominantly hydrophobic)
  • Tend to be extensive in size
  • Tend to close on themselves so that there are no edges with exposed hydrocarbon chains and so they form compartments
  • Self-sealing because a hole in a bilayer is energetically unfavourable
  • Two molecules thick
• Lipid vesicles (liposomes)


  Aqueous compartments enclosed by a lipid bilayer, used to study membrane permeability or to deliver chemicals to cells
• Liposome formation


  Suspending a suitable liquid, such as phosphatidylcholine, in an aqueous medium, and then sonicating (i.e. agitating by high-frequency sound waves) to give a dispersion of closed vesicles that are quite uniform in size
• Membrane proteins


  • Responsible for most of the dynamic processes carried out by membranes
  • Mediate transport of chemicals and information across a membrane
  • Membrane lipids create the appropriate environment for the action of such proteins
• Plasma membranes of most cells are metabolically active and contain many pumps, channels, receptors and enzymes. The protein content of these plasma membranes is typically 50%
• Energy-transduction membranes, such as the internal membranes of mitochondria and chloroplasts, have the highest content of protein, around 75%
• Myelin, a membrane that serves as an electrical insulator around certain nerve fibres, has a low content of protein 18%
• Integral membrane proteins


  • Interact extensively with the hydrocarbon chains of membrane lipids and can be released only by agents that compete for these nonpolar interactions
  • Most integral membrane proteins span the lipid bilayer
• Peripheral membrane proteins


  • Bound to membranes primarily by electrostatic and hydrogen-bond interactions with the head groups of lipids
  • Many are bound to the surfaces of integral proteins, on either the cytoplasmic or the extracellular side of the membrane
  • Others are anchored to the lipid bilayer by a covalently attached hydrophobic chain, such as a fatty acid
• Lipid-anchored membrane proteins

  • Proteins located on the surface of the cell membrane that are covalently attached to lipids embedded within the cell membrane
  • Insert and assume a place in the bilayer structure of the membrane alongside the similar fatty acid tails
• Carbohydrates are associated with both membrane lipids (glycolipids) and proteins (glycoproteins)
• Carbohydrates are exclusively presented on the extracellular side of the plasma membrane (asymmetry)
• Fluid mosaic model


  • Describes the overall organisation of biological membranes: membranes are two-dimensional solutions of oriented lipids and globular proteins
  • The lipid bilayer has a dual role: it's both a solvent for integral membrane proteins and a permeability barrier
  • Membrane proteins are free to diffuse laterally in the lipid matrix unless restricted by special interactions
  • Although the lateral diffusion of membrane components can be rapid, the spontaneous rotation of lipids from one face of a membrane to the other is a very slow process (transverse diffusion or flip-flop)
• Flippases


  Catalyse the rapid flip flop of phospholipids
• Membrane fluidity

  • Influenced by fatty acid composition and saturation
  • Many membrane processes, e.g. transport or signal transduction, depend on the fluidity of the membrane lipids
  • Fatty acid chains can exist in an ordered, rigid state or in a relatively disordered, fluid state
  • The transition from the rigid to the fluid state takes place abruptly as the temperature is raised above the melting temperature
  • The presence of saturated fatty acid residues favours the rigid state
  • A cis double bond produces a bend in the hydrocarbon chain, which interferes with a highly ordered packing of fatty acid chains and so the melting temp is lowered
  • Long hydrocarbon chains interact more strongly than short ones
• Cholesterol

  • Modulates membrane fluidity
  • Inserts into bilayers with its long axis perpendicular to the plane of the membrane
  • Hydroxyl group forms a hydrogen bond with a carbonyl oxygen atom of a phospholipid head group, whereas the hydrocarbon tail is located in the nonpolar core of the bilayer
  • Disrupts the regular interactions between fatty acid chains
  • At low temperatures, prevents phospholipid tight packing and maintains fluidity
  • At warm temperatures, restricts phospholipid diffusion and prevents membranes becoming too fluid
• Cholesterol has many other essential roles, including regulating oxygen entry into eukaryotic cells and organelles, acting as oxygen sensors across all eukaryotic life forms, and serving as a primitive cellular defence against oxygen (including reactive oxygen species)
• Functions of the plasma membrane

  Lipids: Establish semi-permeable barrier between external and internal aqueous environment, provide environment in which proteins can dissolve and function

  Proteins: Cell-cell recognition, signal transduction, transport, enzymatic activity, attachment (cytoskeleton or extracellular matrix), intercellular junctions (adhesion), cell-cell recognition (surface identity marker), determine blood type
• Passive transport


  Simple diffusion: No energy needed, move from high to low concentration towards equilibrium

  Facilitated diffusion: Passive transport aided by proteins, massively speeds up passive movement of molecules, membrane becomes semi-permeable with protein channels/carriers

  Osmosis: Process by which water diffuses across a membrane from the region of lower solute concentration to the region of higher solute concentration to balance the solute concentrations
• Active transport


  Energy input needed (ATP), moves substances from low to high concentration (against concentration gradient), allows cells to maintain concentration gradients that differ from their surroundings