Membrane Composition and Proteins

Membrane Composition

• Lipids are amphiphatic molecules arranged as bilayers with polar groups facing out and nonpolar groups facing in.
• Proteins are surface-associated or embedded in the bilayer.
• Lipids self-associate to form membranes due to the hydrophobic effect.
• Monolayers are single-molecule thick layers at the air/water interface, featuring polar groups interacting with water.
• Micelles are lipid spheres with polar groups oriented outwards and hydrophobic tails positioned centrally.
• Lipid bilayers consist of two lipid monolayers with hydrophobic surfaces facing each other.
• Liposomes are vesicles formed by lipid bilayers.
• The phospholipid bilayer is a flexible, sheet-like structure, described by the fluid mosaic model.

Types of Membrane Proteins

• Peripheral membrane proteins are not strongly bound to the membrane and can be dissociated using mild detergents or high salt concentrations.
• Integral membrane proteins are strongly embedded in the membrane and can be dissociated with strong detergents that denature the membrane.
• Lipid-anchored proteins are covalently attached to a lipid embedded in the membrane.

Types of Integral Membrane Proteins

• TYPE 1 has a C-terminal IN and an N-terminal OUT, featuring an alpha-helix structure.
• TYPE 2 exhibits a C-terminal OUT and an N-terminal IN.
• TYPE 3 contains amino acid loops.
• TYPE 4 consists of separate polypeptide chains.
• TYPE 5 involves a short chain lipid.
• TYPE 6 involves a long chain lipid.

Types of Lipid-Anchored Proteins

• Amide-linked myristoyl anchors use myristic acid (14:0) as the anchor.
• These are linked by an amide to the amino group of N-terminal Gly.
• Thioester-linked fatty acyl anchors use fatty acid as the anchor.
• Prenyl anchors use prenyl (long-chain isoprene polymers) as the anchor.
• Farnesyl is utilized as an anchor.
• Anchors are attached to Cys as a thioester or Ser or Thr as an ester.
• Anchors can be attached as a thioester to Ct Cys.

Glycosyl Phosphatidylinositol

• Glycosyl phosphatidylinositol is an oligosaccharide-modified phosphoinositol used as an anchor.
• Ct is attached via phosphoethanolamine to the Man residue of oligosaccharide.
• The cell membrane is nonpolar.
• The hydropathy plot (Kyte-Doolittle) uses the hydropathy index of amino acids to identify membrane protein topology.
• An increasing number of hydropathy indices means decreasing polarity (or increasing nonpolarity).

Membrane Mobility

• There are two types of membrane mobility: Lateral and Transverse.
• Lateral mobility involves side-to-side movement and is fast.
• Transverse movement goes from the inner to the outer layer (or reverse) and is slow.
• Transverse movement is slower than lateral because the polar head group of lipids must pass through the hydrophobic core of the lipid bilayer.
• This is unfavorable because the hydrophobic interior resists the passage of water-soluble molecules.

Enzymes Assisting in Transverse Movement

• Flippases are ATP-dependent and use energy to move phosphotidyl Serine from the OUTER to INNER surface of the membrane.
• Floppases are ATP-dependent and use energy to move lipids from the INNER to the OUTER surface of the membrane.
• Floppases usually transport cholesterol, phosphotidylcholine, and sphingomyelin.
• Scramblases/Flipfloppases are Ca2+-dependent and ATP-independent, thus not requiring energy.
• They move lipids in either direction, working towards equilibrium.

Membrane Phases and Fluidity

• The Gel Phase (Solid-Ordered State) sees individual molecules unable to move around.
• Lipid chains are extended and closely packed in the gel phase.
• The Liquid Crystalline Phase (Liquid-Disordered State) enables molecules to move around.
• Acyl bonds rotate and bend, membrane thickness decreases, and surface area increases in this phase.
• Membrane fluidity can be varied with temperature.
  • • i. Melting temperature denotes the point at which a phase transition takes place.
  • • ii. An increase in temperature advances the substance from a gel to a liquid phase.
• Membrane fluidity can also be varied with cholesterol.
  • • i. Cholesterol broadens the transition range without altering the melting temperature
  • • ii. At low temperatures, it helps membranes become more rigid.
• Membrane fluidity can also be varied by type of fatty acid.
  • • i. Longer fatty acids favor rigidity and increase melting temperature.
  • • ii. Saturated fatty acids favor rigidity and increase melting temperature.

Types of Membrane Transport

• Passive diffusion is entropy-driven, moves along the gradient (high to low concentration), and is concentration-dependent.
  • Does not involve channels/transporters.
  • Only small, nonpolar molecules are needed in order to pass across the nonpolar membrane.
• Facilitated diffusion is entropy-driven and moves along the gradient (high to low concentration).
  • It is concentration-dependent, saturable, and specific/selective.
  • It involves membrane channels, commonly integral membrane proteins.
• Active Transport is energy-driven, moves AGAINST the gradient, and is specific.
  • Involves transporters, commonly integral membrane proteins.

Types of Passive Diffusion

• Concentration gradient involves differences in concentration between regions.
  • It is a spontaneous process that does not require energy, and energy is released in the process.
• Electrical gradient involves differences in charges between regions.
  • It is also known as electrical potential difference.
• Electrochemical gradient involves differences in concentration and charges.

Facilitated Diffusion

• Channels are transmembrane proteins (integral membrane proteins) that react to chemicals and physical changes in the environment.
  • Voltage-gated channels are activated in response to a change in membrane voltage.
  • Ligand-gated channels are activated in response to a ligand.

Types of Active Transport

• Primary transport uses ATP, light, or redox chains as a source of energy.
  • It involves pumps, and moves AGAINST the gradient.
• Secondary transport uses an ion gradient (driven by ions moving along their gradient).
  • It is also called cotransport.

Types of Cotransport

• Symporters transport a molecule against its gradient along with another molecule moving along its gradient in the same direction.
• Antiporters transport a molecule against its gradient along with another molecule moving along its gradient in the opposite direction.