Membrane Transport

Membrane Structure and Selective Permeability

The plasma membrane is a dynamic boundary that separates the intracellular fluid (ICF) from the extracellular fluid (ECF), maintaining distinct internal conditions through selective permeability. Its structure is closely linked to its function in regulating transport and communication.

• Phospholipids: Amphipathic molecules with hydrophilic heads facing outward and hydrophobic tails inward, forming a bilayer. The hydrophobic core restricts passage of ions and most polar molecules.

• Cholesterol: Modulates membrane fluidity and stability by restraining lipid movement at high temperatures and preventing tight packing at low temperatures.

• Proteins: Serve as transporters, receptors, enzymes, and structural links to the cytoskeleton and extracellular matrix. Integral proteins are embedded within the bilayer; transmembrane proteins span the membrane; peripheral proteins associate with the membrane surface.

• Surface Carbohydrates: Present on glycoproteins and glycolipids, forming the glycocalyx for cell recognition and interaction.

Fluid Mosaic Model: Describes the lateral mobility of lipids and proteins within the membrane, with a diverse array of proteins embedded or associated. Lipid rafts are specialized regions that organize signaling molecules.

• Key Point: Passage through the membrane depends on size, charge, and lipid solubility. Membrane proteins enable selective transport and communication.

Example: Oxygen (O2) and carbon dioxide (CO2) diffuse freely, while ions require specific channels.

Passive Transport and Transport Rate

Passive transport moves substances down their concentration or electrochemical gradients without cellular energy input. The route and rate depend on the substance and membrane properties.

• Simple Diffusion: Direct passage through the lipid bilayer (e.g., O2, CO2, steroid hormones).

• Channel-Mediated Diffusion: Selective pores (channels) allow ions or water (via aquaporins) to cross.

• Carrier-Mediated Diffusion: Solute binds to a carrier protein, which changes shape to transport it (e.g., glucose via GLUT transporters).

• Osmosis: Net movement of water across a selectively permeable membrane, primarily through aquaporins.

Diffusion at Equilibrium: Molecules continue to move randomly, but net diffusion ceases when opposing movements balance.

• Factors Affecting Diffusion: Smaller molecules, higher temperature, steeper gradients, greater permeability, larger surface area, and shorter diffusion distance all increase diffusion rate.

• Channels vs. Carriers: Channels form pores for passive movement; carriers undergo conformational changes and can mediate passive or active transport.

• Carrier Saturation: Transport rate plateaus when all carriers are occupied, regardless of further increases in solute concentration.

Example: Glucose transport via GLUT shows saturation kinetics, while simple diffusion does not.

Active Transport and Coupled Transport

Active transport moves substances against their gradients, requiring energy. It is classified as primary (direct ATP use) or secondary (indirect, using another gradient).

• Primary Active Transport: ATP hydrolysis directly powers transporters (e.g., Na+/K+-ATPase).

• Secondary Active Transport: Uses the downhill movement of one solute (often Na+) to drive the uphill movement of another (e.g., Na+-glucose cotransport).

Sodium–Potassium Pump (Na+/K+-ATPase): For each ATP, moves 3 Na+ out and 2 K+ in, maintaining gradients essential for cell volume, secondary transport, and electrical signaling.

• Cycle: Na+ binds inside → ATP phosphorylates pump → Na+ released outside → K+ binds outside → dephosphorylation resets pump → K+ released inside.

• Electrogenic: Exports one net positive charge per cycle.

Electrochemical Gradient: Net ion flow depends on both concentration and electrical gradients.

• Secondary Active Transport: Symport (same direction) and antiport (opposite directions) describe coupled movement; energy source is the gradient, not direct ATP hydrolysis.

Example: Intestinal Glucose Absorption

1. Basolateral Na+/K+ pump maintains low intracellular Na+.

2. Apical SGLT1 cotransporter brings Na+ and glucose into the cell (secondary active transport).

3. Glucose exits via basolateral GLUT2 (facilitated diffusion).

Key Distinction: SGLT1 uses the Na+ gradient; GLUT2 mediates facilitated diffusion.

Vesicular Transport

Vesicular transport moves large particles or volumes via membrane-bound vesicles, requiring energy. It includes endocytosis (inward) and exocytosis (outward).

• Phagocytosis: Cell engulfs large particles (e.g., microbes) via pseudopodia, forming a phagosome.

• Pinocytosis: Cell samples extracellular fluid and dissolved substances via small vesicles.

• Receptor-Mediated Endocytosis: Specific ligands bind receptors, concentrating cargo for uptake (e.g., LDL, transferrin).

• Exocytosis: Vesicle fuses with plasma membrane, releasing contents outside (e.g., neurotransmitters, hormones).

• Transcytosis: Cargo is transported across a cell via sequential endocytosis and exocytosis.

Receptor-Mediated Uptake: Clathrin-coated pits concentrate specific cargo; vesicles uncoat and sort contents in endosomes. Many receptors are recycled.

Exocytosis Mechanism: SNARE proteins mediate vesicle–membrane fusion. Regulated exocytosis is triggered by signals such as increased intracellular Ca2+.

• Distinctions: Endocytosis brings in; exocytosis releases out. Phagocytosis targets large particles; pinocytosis samples fluid. Receptor-mediated endocytosis is selective.

Example: White blood cells use phagocytosis to engulf bacteria.

Osmosis, Osmolarity, and Tonicity

Osmosis is the net movement of water across a selectively permeable membrane, driven by differences in solute concentration (osmolarity) and solute permeability (tonicity).

• Osmolarity: Total concentration of dissolved particles. Calculated as:

• For mixtures, sum each solute's contribution. (e.g., 0.15 mol/L NaCl: Osm/L = 300 mOsm/L)

• Tonicity: Predicts the sustained effect on cell volume, depending on nonpenetrating solutes and membrane permeability.

• Reference Value: ICF and ECF are typically ~300 mOsm/L in human cells.

Worked Example: 300 mOsm/L NaCl (nonpenetrating) + 100 mOsm/L urea (penetrating) = 400 mOsm/L total. The solution is hyperosmotic but isotonic, as only nonpenetrating solutes determine sustained volume change.

• Osmotic Pressure: The pressure required to prevent net water entry. In a U-tube, hydrostatic pressure can balance osmotic force, stopping net water flow even if concentrations differ.

Problem-Solving Sequence: Count particles → identify solute permeability → compare nonpenetrating concentrations → predict water movement and cell volume. Iso-osmotic does not always mean isotonic.

MCQ Practice: Key Concepts

• Membrane Permeability: The hydrophobic core limits passage of charged ions like Na+.

• Diffusion Equilibrium: Molecules continue moving randomly; net diffusion is zero.

• Electrochemical Gradient: Determines net ion movement through open channels.

• Carrier Saturation: Limited by carrier number and cycling rate.

• Na+/K+-ATPase: 3 Na+ out, 2 K+ in, 1 ATP used per cycle.

• Secondary Active Transport: SGLT1's glucose uptake depends on the Na+ gradient.

• Intestinal Glucose Transport: Apical SGLT1 (secondary active), basolateral GLUT2 (facilitated diffusion).

• Symport vs. Antiport: Coupled solutes in the same direction (symport) or opposite (antiport).

• Phagocytosis: Engulfment of large particles by pseudopodia.

• Receptor-Mediated Endocytosis: Selective binding and concentration of cargo.

• Exocytosis: Vesicle fusion with plasma membrane releases contents.

• Osmolarity Calculation: 0.10 mol/L MgCl2 = 0.10 × 3 = 0.30 Osm/L = 300 mOsm/L.

• Cell Volume Response: Water moves into cells in hypotonic solutions, out in hypertonic, unchanged in isotonic.

• Osmolarity vs. Tonicity: Hyperosmotic solutions can be isotonic if only nonpenetrating solutes are considered.

• Osmotic Equilibrium: Hydrostatic pressure can balance osmotic force, stopping net water flow.

• Iso-osmotic Solutions: If solute is penetrating, solution may be hypotonic despite equal osmolarity.

Additional info: For further study, see Marieb, Human Anatomy & Physiology, 12th edition, Chapter 3, sections 3.2–3.4. Section 3.5 covers the connection between selective ion diffusion and membrane potential.