Cell Membrane: Structure and Membrane Transport

Part 1 - Structure of the Cell Membrane

Overview

The Lipid Bilayer

• Each phospholipid has a hydrophilic phosphate head (faces aqueous environments) and hydrophobic fatty acid tails (face inward, away from water).
• The hydrophobic tails are mutually attracted to one another and form the interior of the bilayer; the hydrophilic heads face the intracellular and extracellular water.
• This middle lipid layer is impermeable to water-soluble substances like ions, glucose, and urea. Fat-soluble substances (O₂, CO₂, alcohol) cross with ease.

• Derived from the amino alcohol sphingosine; also amphipathic.
• Present in small amounts, especially in nerve cells.
• Functions: protection from harmful environmental factors, signal transmission, and adhesion sites for extracellular proteins.

• Highly fat-soluble steroid nucleus; dissolves within the bilayer.
• Controls membrane fluidity and the degree of permeability to water-soluble constituents.

Membrane Proteins

• Protrude all the way through the membrane (transmembrane proteins).
• Most are glycoproteins.
• Functions:
  • Form structural channels (pores) allowing diffusion of water, ions, and small molecules between intracellular and extracellular fluids (with selective properties).
  • Act as carrier proteins for substances that cannot penetrate the lipid bilayer (some transport against electrochemical gradients = active transport).
  • Act as enzymes.
  • Serve as receptors for water-soluble chemicals (e.g., peptide hormones) - ligand binding causes conformational changes that relay signals to the cell interior via second messengers.

• Attached to an integral protein or to one surface only; do not penetrate all the way through.
• Function almost entirely as enzymes or as controllers of transport through membrane pores.

Membrane Carbohydrates - The Glycocalyx

• Glycoproteins (carbohydrate + protein) - most integral proteins are glycoproteins.
• Glycolipids (carbohydrate + lipid) - about 1/10 of membrane lipids.
• Proteoglycans - mainly carbohydrate chains bound to small protein cores, loosely attached to the outer surface.

1. Negative electrical charge (repels other negatively charged objects, prevents cell aggregation).
2. Attaches cells to one another (cell-cell adhesion).
3. Acts as receptors for hormones (e.g., insulin) - activates internal protein cascades.
4. Enters into immune reactions (self/non-self recognition).

Fluid Mosaic Model

• Cholesterol content (more cholesterol = less fluid at physiological temperatures)
• Fatty acid saturation (unsaturated fatty acids increase fluidity)
• Temperature

Part 2 - Membrane Transport

A. Passive Transport

1. Simple (Passive) Diffusion

• Small, non-polar (lipophilic) molecules and gases (O₂, CO₂, N₂, steroid hormones, alcohol) diffuse directly through the lipid bilayer.
• Driven purely by the concentration gradient and kinetic energy of molecules.
• Water crosses very slowly by this route; it mainly uses aquaporins (see below).
• Example: Exchange of O₂ and CO₂ between blood and tissues.

2. Facilitated Diffusion

• Multipass transmembrane proteins form hydrophilic pores.
• Contain a pore domain that partially penetrates the bilayer and acts as an ion-selectivity filter (3D structure determines which ions pass).
• Ion-selective and regulated:
  • Voltage-gated channels - opened/closed by changes in membrane potential (e.g., Na⁺ channels in neurons during action potentials).
  • Ligand-gated channels - opened by binding of a neurotransmitter/chemical (e.g., acetylcholine receptor at neuromuscular junctions).
  • Mechanically gated channels - opened by mechanical stress (e.g., in inner ear hair cells).
• Aquaporins - specialized channel proteins for water transport.

• Carrier proteins bind the substrate specifically, undergo conformational changes, and release the molecule on the other side.
• Highly selective - often transport only one type of molecule.
• Example: Glucose carriers (GLUT transporters).

B. Active Transport

Primary Active Transport

• Na⁺/K⁺-ATPase (sodium-potassium pump): Pumps 3 Na⁺ out and 2 K⁺ into the cell per ATP molecule. Fundamental for maintaining resting membrane potential.
• H⁺ pump (proton pump): Moves H⁺ against its gradient (e.g., in gastric parietal cells for acid secretion, in mitochondria).
• Ca²⁺-ATPase: Pumps Ca²⁺ out of the cytoplasm.

Secondary Active Transport (Co-transport)

• Symport (co-transport): Both Na⁺ and the molecule move in the same direction (e.g., Na⁺/glucose co-transporter in intestinal epithelium).
• Antiport (counter-transport/exchange): Na⁺ and the molecule move in opposite directions (e.g., Na⁺/H⁺ exchanger).

Transporter Superfamilies

• ABC (ATP-Binding Cassette) transporters: Primary active transporters using ATP hydrolysis. ~2000 transporter genes = ~7% of the human genome. Key examples: P-glycoprotein (Pgp/ABCB1, MDR1) - effluxes drugs; CFTR (ABCC7) - chloride channel mutated in cystic fibrosis.
• SLC (Solute Carrier) superfamily: ~65 families with ~460 transporters; includes facilitated and secondary active transporters. Critical for drug absorption and elimination.

C. Vesicular Transport

Endocytosis (substances enter the cell)

1. Phagocytosis ("cell eating") - engulfment of large particles (bacteria, debris) by pseudopod extension; primarily in macrophages and neutrophils.
2. Pinocytosis ("cell drinking") - non-specific uptake of extracellular fluid and small solutes in small vesicles.
3. Receptor-mediated endocytosis - the most selective form; specific ligands bind to membrane receptors concentrated in clathrin-coated pits, which invaginate to form coated vesicles. Example: LDL cholesterol uptake via LDL receptors.

Exocytosis (substances leave the cell)

• Intracellular vesicles (from Golgi apparatus) fuse with the plasma membrane, releasing cargo into the extracellular space.
• Primary secretory pathway for hormones, neurotransmitters, enzymes, and antibodies.
• Mediated by SNARE proteins that facilitate vesicle-membrane fusion.
• Exocytosis and endocytosis are coupled - blocking one (e.g., tetanus/botulinum toxins block exocytosis via SNARE proteins) also blocks the other; this prevents secretory cells from swelling or shrinking.

Summary Table: Membrane Transport Mechanisms