Membrane Structure and Transport — Comprehensive Study Notes

Membrane structure and functions

• Functions of membranes (recap):
  • Define boundaries of the cell and internal compartments (e.g., mitochondria)
  • Serve as sites for biochemical functions (e.g., electron transport in mitochondria)
  • Transport solutes in and out of the cell (selective permeability)
  • Detect and transmit electrical and chemical signals
  • Provide mechanisms for cell-to-cell contact, adhesion and communication
• The membranes’ distribution: identify where membranes are in cellular images (conceptual question from slides)

Fluid mosaic model

• Proposed in the 1970s
• Fluid: lipids and proteins can move within the plane of the membrane
  • Lateral movement (side-to-side)
  • Rotation around the axis
  • Flip-flop (transverse movement) is rarer
• Mosaic: diverse proteins and lipids dispersed within the lipid bilayer
• Overall: dynamic, two-dimensional fluid of lipids with embedded proteins

Organisation of the membrane

• Phospholipid bilayer is the core structure
• Composed of lipids, proteins, and carbohydrates; protein:lipid ratios vary among membranes
• Example ratios in mitochondria:
  • Outer mitochondrial membrane: $1.2:1$ (protein:lipid or lipid:protein ratio context-dependent in slides)
  • Inner mitochondrial membrane: $3.5:1$ (higher protein content)
• Polar (hydrophilic) head groups face aqueous environments; non-polar (hydrophobic) tails face inward

Membrane lipids: three main classes

1) Phospholipids (most abundant)

• Backbone moiety with polar head attached to a phosphate group; non-polar fatty acid tails
• Major subtypes: phosphoglycerides and phosphosphingolipids
• Amphipathic nature: polar head (charged) and non-polar tails
• Polar head components and variability
  • Polar head contains phosphate group and variable R group (such as choline, serine or inositol)
  • Charged, hydrophilic (polar)
• Backbone options: glycerol or sphingosine
• Tails: long unbranched hydrocarbon chains with carbonyl group; can be saturated or unsaturated
  2) Glycolipids
• Lipids with carbohydrate groups attached
• Examples: glycoglycerolipids and glycosphingolipids
• Roles in signalling and as molecular markers
• E.g., glycosphingolipids used as cell-surface markers (e.g., blood group antigens)
  3) Sterols
• Have four-ring hydrocarbon structure
• Examples: cholesterol (animal membranes) and phytosterols (plants)

Phospholipid structure (phosphoglycerides and related phospholipids)

• Phospholipids are amphipathic
• Components:
  • Polar head: phosphate group + variable R group; hydrophilic (polar)
  • Backbone: glycerol (or sphingosine in sphingolipids)
  • Non-polar tails: fatty acids; hydrophobic
• Two main types of phospholipids
  • Phosphoglycerides (glycerophospholipids)
  • Phosphosphingolipids (sphingophospholipids)

Fatty acids and membrane fluidity

• Fatty acids have saturated or unsaturated chains
  • Saturated fatty acids: single bonds; straight chains
  • Unsaturated fatty acids: one or more double bonds; bends/kinks
  • Double bonds cause kinks that prevent tight packing, maintaining fluidity
• Consequences:
  • Saturated fats tend to pack tightly and solidify at room temperature
  • Unsaturated fats remain more fluid
• Examples:
  • Saturated: Palmitic acid, stearic acid
  • Unsaturated: Oleic acid, linoleic acid
• Visual takeaway: structure with bends leads to looser packing and a more fluid membrane

Membrane lipids: more on classifications

• Glycolipids are abundant on the outer leaflet and participate in recognition/signalling
• Sterols (cholesterol in animals, phytosterol in plants) modulate membrane fluidity and permeability
• The cholesterol question: Is cholesterol good or bad?
  • It is not inherently good or bad; it modulates membrane properties
  • In membranes, cholesterol can reduce permeability to small molecules and maintain appropriate fluidity; context matters

Membrane carbohydrates (glycoconjugates)

• Oligosaccharides attached to proteins (glycoproteins) or lipids (glycolipids)
• Roles:
  • Signalling
  • Molecular markers for recognition (antigenic determinants)
• Examples:
  • Glycosphingolipids with A and B antigens (blood group markers)

Membrane proteins: categories and organization

• Membrane proteins are a mosaic component of the fluid mosaic model
• Major classes (based on attachment to the membrane):
  • Integral proteins: embedded within the lipid bilayer; hydrophobic regions interact with lipids
  • Can be monotopic (partially embedded) or transmembrane (spanning the bilayer)
  • Peripheral proteins (extrinsic): lack hydrophobic sequences; often on the membrane surface; e.g., some enzymes
  • Lipid-anchored proteins: hydrophilic proteins attached via lipid anchors (e.g., GPI-anchored proteins)

Membrane protein functions

• Transport: channels and carriers for solute movement
• Ion homeostasis
• Enzymatic activity and localization of metabolic pathways (e.g., ETC and ATP production clamping at membranes)
• Signal transduction: receptors bind signalling molecules and relay messages
• Cell-to-cell recognition: surface markers for identification
• Cell junctions: “glue” cells together for barrier function
• Structural attachment: link to cytoskeleton and extracellular matrix

Selective permeability of membranes

• Membranes are hydrophobic barriers to most ions and large molecules
• Permeable to small nonpolar molecules and gases (e.g., O2, CO2) with varying water permeability
• Hydration water (H2O) permeates but more slowly than gases
• Hardly permeable to larger molecules (>$100 ext{ MW}$)
  • Example: glucose with MW ≈ $180 ext{ Da}$ is poorly permeable without transport proteins
• Most hydrophilic solutes require transport proteins to cross the membrane

Transport across membranes: general categories

• Passive transport
  • Simple diffusion
  • Facilitated diffusion (via channels or carriers)
• Active transport
  • Requires energy (ATP) and a pump
• The classic erythrocyte transport diagram illustrates these processes ((a) simple diffusion of O2/CO2/H2O, (b) facilitated diffusion of glucose via carrier, (c) facilitated diffusion of water via aquaporin, (d) Na+/K+ ATPase pump active transport)

Passive transport: simple diffusion

• Movement from high concentration to low concentration
• Bidirectional, determined by concentration gradient
• No energy input required
• Does not require a membrane protein
• Generally slow; may not meet cellular needs for rapid transport
• Examples: gases like O2 and CO2

Osmosis

• Diffusion of water across a selectively permeable membrane
• Driven by relative osmolarity (solute concentration inside vs outside)
• Different species have different cellular osmolarities
• Hypertonic: higher solute outside; water moves out of the cell
• Isotonic: equal solute concentration; no net water movement
• Hypotonic: higher solute inside; water moves into the cell
• Reflects how cells respond to changes in osmolarity (animal vs plant cells)

Facilitated diffusion

• Requires membrane proteins (channel or carrier)
• Provides selective permeability for specific solutes
• Flow from high concentration to low concentration
• Faster than simple diffusion but can saturate at high solute concentrations
• Does not require energy
• Temperature-sensitive
• Example: glucose transport via carrier proteins

Active transport

• Requires membrane pump and energy (ATP)
• Moves solutes against their concentration gradient
• Critical for uptake of scarce essential nutrients and removal of waste
• Maintains intracellular ion gradients (e.g., Na+, K+, Cl−)
• Example: Na+/K+ pump (Na+ expelled, K+ taken in)

Types of membrane transport by solute directionality

• Uniport: single solute transported in one direction
• Symport: two or more solutes transported in the same direction (coupled transport)
• Antiport: two or more solutes transported in opposite directions

References and further reading

• Textbook chapters: Chapter 7 Membranes: Their Structure, Function, and Chemistry; Chapter 8 Transport Across Membranes: Overcoming the Permeability Barrier
• Becker’s World of the Cell (9th edition, various figures referenced in slides)
• Additional figures and resources cited (e.g., Glycosphingolipids, transport models, and membrane protein structures)

Practical implications and real-world relevance

• Membrane composition directly affects cell signaling, energy generation, and transport efficiency
• Protein composition and lipid environment influence receptor function, ion pumps, and transporters
• Understanding membrane transport is essential for pharmacology (drug uptake, targeting transporters), physiology (nerve impulses, osmoregulation), and pathology (membrane defects, transport disorders)

Quick recap of key numbers and terms (for rapid revision)

• Outer mitochondrial membrane vs inner mitochondrial membrane protein:lipid ratios: $1.2:1$ vs $3.5:1$
• Largest class of membrane lipids: phospholipids (phosphoglycerides and phosphosphingolipids)
• Three main lipid classes: Phospholipids, Glycolipids, Sterols
• Major carbohydrate markers: glycosphingolipids (e.g., A and B antigens in blood groups)
• Common small solutes that diffuse passively: O2, CO2
• Water diffusion: slower than gases; aquaporins facilitate rapid water transport
• Glucose: MW ≈ $180$ Da
• General permeability rule: charged ions (H+, Na+, K+, Cl−) are largely impermeable without transport proteins
• Also note: facilitated diffusion is saturable and temperature-sensitive; active transport requires energy and pumps (e.g., Na+/K+ ATPase)