3.1.1 Biological Membrane Architecture

1. The Fluid Mosaic Model (Singer–Nicolson, 1972)
2. Phospholipid Bilayer:
   • Amphipathic Nature: Hydrophilic head (phosphate + glycerol), hydrophobic fatty acid tails.
   • Bilayer Arrangement: Two leaflets—extracellular (outer) leaflet and cytosolic (inner) leaflet—create a hydrophobic core ~3–4 nm thick.
3. Integral (Intrinsic) Proteins:
   • Span the bilayer (transmembrane proteins).
   • Often α-helical segments composed of hydrophobic amino acids within the membrane’s core.
   • Roles: transport channels, carriers, receptors, enzymes.
4. Peripheral (Extrinsic) Proteins:
   • Loosely bound to the membrane’s surface via ionic or hydrogen bonds (e.g., cytoskeletal attachments, signaling complexes).
5. Glycocalyx: Carbohydrate chains (glycoproteins, glycolipids) present on the extracellular leaflet; important for cell–cell recognition, protection, and adhesion.
6. Lipid Composition and Membrane Properties
7. Phospholipid Diversity:
   • Phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI) have distinct head groups with specific functions:
   • PC/PE: Abundant in eukaryotic plasma membranes.
   • PS: Normally on inner leaflet; “flip” to outer leaflet signals apoptosis.
   • PI: Can be phosphorylated to form PIP, PIP₂—critical for signaling cascades.
8. Cholesterol (in Animal Cells):
   • Intercalated between phospholipids; reduces membrane permeability to small water-soluble molecules.
   • Modulates fluidity by preventing phospholipid tails from packing too closely at low temperatures and restricting excessive motion at high temperatures.
9. Sphingolipids (e.g., Sphingomyelin, Glycosphingolipids):
   • Contain a sphingosine backbone.
   • Enriched in the outer leaflet of the plasma membrane, often concentrated in lipid rafts.
10. Membrane Asymmetry and Leaflet Composition

3.1.2 Membrane Transport Mechanisms

Biological membranes are selectively permeable, allowing some substances to cross freely while restricting others. Transport can be passive (no energy expenditure) or active (requires energy, usually ATP).

1. Passive Transport (Downhill Movement, no ATP)
2. Simple Diffusion:
   • Nonpolar, small uncharged molecules (O₂, CO₂, N₂, steroid hormones) dissolve in lipid bilayer and diffuse across.
   • Driven by concentration gradient (high → low).
3. Facilitated Diffusion:
   • Polar or charged molecules (glucose, ions) require specific membrane proteins:
   • Channel Proteins (Ion Channels): Provide hydrophilic pores. Can be gated (voltage-gated, ligand-gated, mechanosensitive).
   • Carrier Proteins (Transporters): Undergo conformational change to translocate substrate (e.g., GLUT transporters for glucose).
   • Example:
     • GLUT1 – ubiquitous glucose transporter in erythrocytes and blood–brain barrier.
     • GLUT4 – insulin-responsive transporter in muscle and adipose tissue.
4. Osmosis:
   • Passive movement of water from region of lower solute concentration to region of higher solute concentration via aquaporins (specialized water channels) or directly through lipid bilayer (slowly).
   • Osmotic Pressure: Pressure required to stop water movement across semi-permeable membrane.

1. Active Transport (Uphill Movement, Requires Energy)
2. Primary Active Transport:
   • Directly uses ATP hydrolysis to move substances against gradient.
   • Examples:
     • Sodium–Potassium ATPase (Na⁺/K⁺ Pump): Maintains high [K⁺] (inside) and high [Na⁺] (outside). For every ATP hydrolyzed, 3 Na⁺ exported, 2 K⁺ imported → electrogenic (net –1 charge inward).
     • Ca²⁺ ATPase (SERCA in sarcoplasmic reticulum): Sequesters Ca²⁺, essential for muscle relaxation.
     • H⁺ ATPase (in plant vacuoles, fungi, bacteria): Pumps protons to acidify compartments or generate proton-motive force.
3. Secondary Active Transport (Cotransport):
   • Symport (Cotransport in the same direction): Uses downhill movement of one solute (e.g., Na⁺) to drive uphill transport of another (e.g., glucose). Example: Sodium-glucose cotransporter (SGLT) in intestinal epithelial cells.
   • Antiport (Exchanger): One solute moves down gradient, another moves opposite/uphill. Example: Na⁺/Ca²⁺ exchanger in cardiac muscle helps extrude Ca²⁺.
   • Relies on gradients established by primary transporters.
4. Energy Coupling:
   • ATP hydrolysis by primary pumps generates electrochemical gradients that store potential energy.
   • Secondary transport harnesses that energy without directly requiring ATP at transporter site.

3.1.3 Bulk Transport (Vesicular Trafficking)

1. Endocytosis: Uptake of large particles, fluid, or macromolecules by invagination of plasma membrane to form vesicles.
2. Phagocytosis (“Cell Eating”): Engulfment of large particles (bacteria, cell debris) into a phagosome. Common in macrophages and neutrophils. Phagosome fuses with lysosome for degradation.
3. Pinocytosis (“Cell Drinking”): Nonspecific uptake of extracellular fluid and dissolved solutes into small vesicles.
4. Receptor-Mediated Endocytosis (RME):
   • Specific ligands (e.g., LDL, transferrin) bind cell surface receptors.
   • Coated pits (clathrin-coated) invaginate, forming clathrin-coated vesicles.
   • After internalization, vesicles uncoat, fuse with early endosomes.
   • Ligands either sorted for degradation in lysosomes or recycled.
5. Exocytosis:
6. Vesicles (e.g., secretory vesicles in neurons, endocrine cells) fuse with plasma membrane to release contents extracellularly.
7. SNARE Proteins (v-SNARE on vesicle, t-SNARE on target membrane): Mediate specific vesicle fusion.
8. Regulated Exocytosis: Requires a trigger (e.g., Ca²⁺ influx in synaptic vesicle release).
9. Constitutive Exocytosis: Continuous, unregulated release of extracellular matrix proteins, membrane proteins.

3.1.4 Membrane Potential and Electrochemical Gradients

• Resting Membrane Potential (RMP):
• Typically –60 to –90 mV (inside negative relative to outside) in animal cells.
• Determined by differential permeability to K⁺, Na⁺, Cl⁻, and the activity of Na⁺/K⁺ ATPase.
• Nernst Equation: Calculates equilibrium potential for a single ion:

E_{ion} = rac{RT}{zF} ext{ln}igg(rac{[ ext{ion}]{ ext{outside}}}{[ ext{ion}]{ ext{inside}}}igg)

• R = universal gas constant; T = temperature (K); z = valence; F = Faraday’s constant.
• Electrogenic Pumps:
• Na⁺/K⁺ ATPase contributes directly to RMP by exporting +1 net positive charge per cycle.
• Electrochemical Gradient:
• Combined effect of concentration (chemical) gradient and electrical gradient (membrane potential) drives ion movement.
• Significance:
• RMP is essential for excitability of neurons and muscle cells.
• Establishes proton gradients in mitochondria/chloroplasts (proton-motive force) for ATP synthesis.