cellmol 4-6

• Membranes serve as the boundary between the cell and its environment
• Critical for cell membrane to exhibit selective permeability
• Organization and localization of function in organelle membranes contain transport proteins that regulate entry and exit of compounds
• Transport processes and cell to cell interactions
• Able to mediate communication but within adjacent cells only
• Signal detection for long-range signaling
• Cell needs to receive and interpret signals such as hormones
• Cell detects insulin to increase glucose transporters in cell membrane for greater capability to process glucose
• Membrane composition includes lipids, proteins, and carbohydrates
• Lipids are the main composition and contribute to selective permeability and water entry regulation
• Proteins are involved in transport processes where small, nonpolar, and uncharged compounds get in free
• Carbohydrates are for signal transduction and detection, such as antigens in blood
• Models of membrane structure and experimental approaches
• Overton observed that lipids are present on the cell surface as a "coat" which are a mixture of phospholipids and cholesterol
• Langmuir concluded that phospholipids orient themselves on water with hydrophilic heads facing the water and hydrophobic tails protruding away
• Gorter and Grendel concluded that erythrocyte plasma membrane consists of two layers of lipids
• Davson and Danielli recognized the importance of proteins in membrane structure and proposed a "sandwich" model
• Robertson observed that subcellular organelles are bounded by similar membranes with a "railroad track" pattern
• Shortcomings of the Davson-Danielli model include thickness of membranes, inconsistency in protein shapes, variability in membrane composition, effect of phospholipases, and insolubility of membrane proteins
• Fluid mosaic model with a mosaic of proteins in a lipid bilayer
• Fluid lipid bilayer with hydrophilic heads oriented outwards and tails inwards, remaining intact due to weak noncovalent interactions
• Fluidity of the membrane is crucial for the cell to survive and is rooted in hydrophobic interactions between phospholipids
• Proteins in the model are involved in transport and signal recognition, with types including integral proteins, peripheral proteins, and lipid-anchored proteins
• Lipid anchored proteins:

  • Located in a similar region of the peripheral protein
  • Covalently linked to a fatty acid embedded in the bilayer
  • Undergo palmitoylation:
  • Post translational modification where a palmitoyl group (16 carbon fatty acid) is covalently attached
  • Embedded in the membrane bilayer core
• Membranes are not homogenous but freely mixing due to embedded proteins

  • Some regions of the membrane are densely populated with proteins while others are not
  • Membranes are ordered through dynamic microdomains called lipid raft
• Membrane fluidity:

  • Characterized by having individual phospholipid units free to move within their respective monolayer
  • Free to rotate and move laterally within the confines of the monolayer
  • Transverse diffusion/flip flops:
  • Movement of one monolayer to another
  • Hydrophilic head moves through the hydrophobic layer of the membrane
  • Energetically unfavorable but important in membrane synthesis
• Membranes: Lipids 1 (Structure):

  • Main component of the cell membrane
  • Membrane contains several major classes of lipids
  • Main classes of membrane lipids are phospholipids, glycolipids, and sterols
• Phospholipids:

  • Amphipathic with both polar and nonpolar regions
  • Glycerophospholipid:
  • Glycerol backbone with fatty acids covalently attached
  • Phosphate group attached at the other end with variations in fatty acid and polar group
  • Sphingolipid:
  • Glycerol backbone replaced with sphingosine
  • Composition of membrane lipids varies depending on the organism and organelle
  • Fatty acids are components of all membrane lipids except sterols
• Glycolipids:

  • Formed by the addition of carbohydrates to lipids
  • Some are glycerol-based, some are Sphingolipid-based
  • Common types include cerebroside and ganglioside
• Sterols:

  • Membranes of most eukaryotes contain significant amounts of sterols
  • Cholesterol in animals stabilizes the membrane
  • Phytosterol in plants and ergosterol in bacteria
  • In bacteria, cholesterol analogues like hopanoids are used
  • Hopanoids share the same structure as those in cholesterol and phytosterol, highlighting the essential role of sterols in stabilizing the membrane
• • Cis double bonds increase fluidity by introducing bends or kinks, avoiding close packing
  • Most plasma membrane fatty acids vary in length and degree of unsaturation to ensure fluidity at physiological temperatures
• Membrane Fluidity:

  • Membranes are fluid at physiological temperatures and conditions
  • Most unsaturated fatty acids contain cis double bonds
  • Commercially produced trans fats are packed together
• Effects of Fatty Acid Composition on Membrane Fluidity:

  • Intercalation of rigid cholesterol molecules into a membrane decreases fluidity and increases the transition temperature
  • Cholesterol prevents hydrocarbon chain packing tightly, reducing membrane tendency to gel upon cooling
  • Cholesterol acts as a fluidity buffer to regulate membrane fluidity in response to external factors like temperature
  • Sterols can regulate membrane fluidity from both ends of a spectrum, preventing the membrane from becoming too fluid or too rigid
• Regulation of Fluidity:

  • Organisms can regulate membrane fluidity by varying lipid composition
  • Poikilotherms use homeoviscous adaptation to compensate for temperature changes by altering fatty acid length and saturation
  • Marr & Ingraham (1962) demonstrated that temperature changes affect lipid composition in membranes
• Membrane Asymmetry:

  • Lipids are distributed unequally between the two monolayers
  • Glycolipids in animal cells are mostly in the outer layer for cell signaling and reception
  • Membrane asymmetry is established during membrane synthesis and remains relatively constant
• • Cavin dissociation from the caveolin-cavins complex can influence gene expression, particularly genes involved in cell membrane repair in response to mechanical stress
• Lipid Rafts:

  • Membranes are not homogenous and contain microdomains like lipid rafts
  • Lipid rafts are densely populated with proteins and biomolecules, involved in various cellular processes
  • Caveolae are small invaginations of the plasma membrane enriched with cholesterol, sphingolipids, and lipid-anchored proteins
  • Caveolae play roles in endocytosis, exocytosis, redox sensing, and regulation of lung airway factor
  • Caveolae invagination is crucial for receiving materials into the cell and sensing mechanical force