Cell Membrane I - Biophysics 5

• Plasma membrane


  The outermost part of the cell (in animals) and forms a barrier between the cell and the outside world
• Plasma membrane


  • Composed of a phospholipid bilayer embedded with proteins
  • Selectively permeable barrier - regulating which molecules enter and which leave
  • Serves as a communication channel which the cell uses to send and receive signals from other cells
• Lipids


  Soluble in hydrophobic (fat) rather than hydrophilic (water) solvents
• Lipids


  • Important components of all cell membranes
  • Used as an energy store and in thermoregulation
  • Some have roles in signalling within and between cells
• Common types of lipids

  • Fatty acids
  • Triglycerides
  • Phospholipids
  • Sterols and steroids
• Fatty acid


  Consists of a carboxylic acid group with a long carbon chain
• Fatty acids


  • The tail can range in length from ~2 to ~30 Carbons and may be saturated or unsaturated
  • Hydrogenation involves adding hydrogen to saturate the chains

  
• Common fatty acids


  • Palmitic acid (16:0)
  • Stearic acid (18:0)
  • Oleic acid (18:1) (monounsaturated)
  • Arachidonic acid (20:4) (polyunsaturated)
• Omega number


  Denotes where the double bond is, counted from the omega end
• Cis and trans configurations

  Cis configuration causes the chain to become kinked, trans configuration is more common in processed foods
• Essential and non-essential fatty acids

  Only 2 fatty acids are known to be essential for humans
• Triglycerides


  Fatty acids found in complex with glycerol
• Triglycerides


  • The carbon tails may be different or all the same
  • High levels in human blood are linked to heart disease
• Phospholipids


  Form the basis of all cell membranes and are one of the most important bio-molecules
• Phospholipids


  • Have two fatty acid tails - can both be the same or different
  • Are amphipathic molecules with a polar hydrophilic head and non-polar hydrophobic tails
• Common phospholipid head groups

  • Choline
  • Ethanolamine
  • Serine
  • Inositol
• Phospholipid bilayer formation


  1. Hydrophobic force minimises contact between water and hydrophobic tails

  2. Phospholipids form either liposomes (lipid bilayer) or micelles depending on head-to-tail size ratio
• Phospholipid bilayers


  • The barrier between inside and outside the cell is only 2 molecules thick
  • Bilayer experiences different stress and repulsion regimes across the plane
• Liquid and solid phases of phospholipid bilayers

  Liquid phase has high lipid lateral mobility and disordered tails, solid phase has low mobility and ordered tails

  
• Cholesterol


  A sterol incorporated into cell membranes to regulate fluidity
• Cholesterol


  • Its small hydrophilic head means it likes to shelter underneath phospholipid head groups
  • Its flat rigid ring structure imposes order on nearby phospholipid tails
• Bilayer phases


  • Liquid-disordered
  • Liquid-ordered
  • Solid-ordered
• Steroid


  A type of lipid
• Sterol


  A type of steroid
• Cholesterol


  A type of sterol that is incorporated into cell membranes and accounts for up to 30% of the mammalian cell plasma membrane (by mole). Its job is to regulate membrane fluidity. Intracellular membranes contain lower concentrations of cholesterol
• Other sterols


  • Testosterone
  • Oestrogen
• Cholesterol


  • Its small hydrophilic head means it likes to shelter underneath the phospholipid head groups
  • The ring structure is flat and inflexible, meaning it imposes order of nearby phospholipid tails
• Bilayer phases


  • Liquid-disordered phase
  • Liquid-ordered phase
  • Solid-ordered phase
• Unsaturated lipids


  Liquid-disordered phase
• Saturated lipids


  Solid-ordered phase

  
• Cholesterol


  Liquid-ordered phase
• Liquid-disordered phase


  High lipid lateral mobility, thinner bilayer, low lipid tail order
• Liquid-ordered phase


  High lipid lateral mobility, thicker bilayer, high lipid tail order
• Solid-ordered phase


  Low lipid lateral mobility, thicker bilayer, high lipid tail order
• In artificial membranes, it is easy to make bilayers showing liquid-ordered, liquid-disordered phase immiscibility. Lipids segregate based on their affinity for each phase

  
• In cells, due to the added complexity of 1000s of lipids and proteins, ordered phase domains are though to be small (10s of nm) and highly transient (existing for a few ms at a time)
• Hydrophobic mismatch energy


  The energy cost of having a membrane protein with a hydrophobic thickness that does not match the hydrophobic thickness of the surrounding lipid bilayer
• Types of membrane proteins

  • Transmembrane proteins
  • Lipid anchored proteins
  • Peripheral proteins
• Membrane proteins


  • They perform many functions – water channels, ion channels, adhesion molecules, hormone receptors
  • Membrane proteins represent 30% of all known proteins but they are among the most difficult to get accurate structures for
  • The vast majority of (legal and illegal) drugs target the function of membrane and membrane-associated proteins
  • They account for up to 20-30% of mammalian cell membrane by area. The cell membrane is therefore often called a lipid-protein composite
• Membrane protein arrangements


  • Single trans-membrane domain
  • Multiple trans-membrane domains
  • Post-translational modification (acylation)
  • Post-translational modification (glycophosphatidylinositiol (GPI)-anchored
  • Intracellular peripheral membrane protein
  • Extracellular peripheral membrane protein