The membrane,
barrier, gate and energy user.

View full size

Close

Phospholipids are amphipathic: a hydrophilic phosphate head faces water on either side, while two hydrophobic fatty-acid tails pack together to form the bilayer core. Each leaflet is a mirror image of the other, so the bilayer is a two-layer sandwich with hydrophilic surfaces and a hydrophobic centre — the arrangement that makes the membrane a barrier to water-soluble and charged solutes at the same time as it stays fluid enough for proteins to move within it.

Composition: phospholipids, cholesterol, proteins and carbohydrates

Cholesterol’s effect on fluidity is temperature-dependent, and the direction matters. Above the membrane’s phase-transition temperature, phospholipid tails are relatively disordered and mobile; cholesterol’s rigid steroid ring system wedges between them, restricts their movement and reduces fluidity. Below the phase-transition temperature, tails would otherwise pack tightly into an ordered, gel-like state; cholesterol disrupts that close packing and increases fluidity, preventing the membrane from becoming too rigid. The net effect is that cholesterol narrows the temperature range over which the membrane’s fluidity changes sharply — it acts as a buffer, keeping the bilayer in a workable intermediate state rather than letting it swing between a rigid gel and an overly fluid liquid as temperature changes. This is why cholesterol content, not just temperature, has to be considered whenever membrane function is discussed across a temperature range, from deliberate intraoperative hypothermia to fever.

Small, uncharged, lipid-soluble molecules (O₂, CO₂, volatile anaesthetic agents, steroid hormones) cross the bilayer directly and rapidly. Water crosses faster than its lipid solubility alone predicts, mainly through aquaporin channels rather than through the lipid itself. Ions and polar solutes (Na⁺, K⁺, Ca²⁺, glucose, amino acids) are essentially excluded from the hydrophobic core and depend entirely on the transport proteins covered in the rest of this lesson.

Equivalently, permeability can be expressed as P = K·D/Δx, where K is the lipid:water partition coefficient, D is the diffusion coefficient within the membrane and Δx is membrane thickness: a higher partition coefficient or diffusion coefficient increases diffusion, whereas a thicker membrane reduces it. Small molecules and low-viscosity media generally have higher diffusion coefficients. Charge and ionisation reduce simple diffusion through lipid, because a charged species partitions poorly into a hydrophobic core.

Predict what happens if: a burn or inflammation doubles capillary surface area available for exchange, with everything else unchanged — flux roughly doubles, since ṅ is directly proportional to A.

Facilitated diffusion is passive despite requiring a carrier: glucose moves down its electrochemical gradient through GLUT transporters without any ATP being spent. Because the number of carrier molecules is finite, facilitated diffusion shares three properties with every other carrier-mediated process in this lesson (including the pumps in the next section):

• Specificity — a carrier recognises a defined solute or closely related family of solutes, unlike the bilayer itself, which discriminates only by lipid solubility, size and charge.
• Saturation — rate rises with concentration only until every carrier is occupied, at which point the rate plateaus at a transport maximum (Tmax), no matter how much further the gradient steepens.
• Competition — a structurally similar molecule can occupy the same binding site and reduce the transport rate of the solute you are interested in.

Predict what happens if: extracellular glucose concentration is pushed far above the physiological range — facilitated glucose entry via GLUT approaches its transport maximum and stops rising in proportion, unlike simple diffusion of a lipid-soluble gas, which keeps rising linearly with the gradient.

The sodium–potassium adenosine triphosphatase (Na⁺/K⁺-ATPase) moves three sodium ions out and two potassium ions in for each ATP hydrolysed. It is electrogenic (the unequal 3:2 exchange contributes a small direct current), but its dominant physiological importance is maintaining the sodium and potassium concentration gradients that everything else in this module depends on: cell-volume regulation, the resting membrane potential and, through secondary active transport, the uphill movement of glucose, amino acids and calcium.

Sarco/endoplasmic reticulum Ca²⁺-ATPase (SERCA) uses ATP directly to sequester calcium into the endoplasmic or sarcoplasmic reticulum; the plasma-membrane Ca²⁺-ATPase extrudes calcium from the cell by the same primary-active mechanism. Both keep resting cytosolic calcium roughly four orders of magnitude below extracellular calcium — the steep gradient that makes calcium useful as a fast intracellular signal (developed further in the signalling lesson).

Secondary active transport spends, rather than creates, a gradient. The sodium-glucose cotransporter (SGLT) uses the inward electrochemical pull on Na⁺ (built by the Na⁺/K⁺-ATPase) to drag glucose uphill into the cell — a symporter, because both solutes move the same direction. The Na⁺/Ca²⁺ exchanger uses the same stored sodium gradient to extrude calcium — an antiporter, because the two solutes move in opposite directions. Neither hydrolyses ATP itself; both stop working if the Na⁺/K⁺-ATPase is poisoned (for example by a cardiac glycoside indirectly raising intracellular Na⁺), which is why “active transport” is defined by the direction of net movement against a gradient, not by which specific step consumes ATP.

All seven routes across the membrane, compared

Every mechanism in this lesson answers the same four questions differently: what carries the solute, which way it moves relative to its gradient, whether it saturates, and where the energy comes from. Read across a row before comparing rows — the pattern that matters for the exam is which properties travel together (saturation, specificity and competition are a package; simple diffusion and filtration are the only two that have none of them).

Vesicular transport shares one feature with primary active transport and none with simple diffusion: it is an energy-dependent, cellular process (vesicle budding, cytoskeletal transport and fusion machinery all consume ATP or GTP), and — unlike every other process in this lesson — it moves bulk cargo rather than individual solute molecules one at a time.

Urea contributes to measured osmolality but exerts little sustained tonic effect on most cell membranes, because it eventually equilibrates across them (a low reflection coefficient) — a rise in plasma urea alone does not sustainedly shrink cells the way an equivalent rise in an impermeant solute would. Sodium salts, largely excluded from cells by the Na⁺/K⁺-ATPase, remain effective extracellular osmoles and do determine sustained cell volume. Acute water movement (the immediate osmotic response) and the eventual steady state (once any permeant solute has redistributed) can therefore differ substantially for the same starting osmolality.

Hypotonic extracellular fluid drives net water entry and cell swelling; in the brain, this can worsen cerebral oedema — one reason hypotonic intravenous fluids are avoided in neurological injury. Hypertonic extracellular fluid drives net water loss and cell shrinkage, the basis for using hypertonic saline or mannitol (a non-penetrating solute at the blood-brain barrier) to draw water out of brain tissue and reduce intracranial pressure.

Take-home points for this lesson. The bilayer’s hydrophobic core is the barrier; lipid solubility predicts what crosses it unassisted, and that same relationship (the Meyer–Overton correlation) is the historical basis for the lipid theories of anaesthesia, now superseded by protein-target theories that still respect the correlation. Every carrier-mediated process — facilitated diffusion, primary active transport, secondary active transport — is specific, saturable and competitively inhibited; only simple diffusion and filtration are not. Active transport is defined by movement against a gradient, not by which step spends the ATP. Osmolarity counts particles; tonicity depends on the reflection coefficient of each particle at that particular membrane.