Cell Membranes and Transport

Fluid Mosaic Model

The fluid mosaic model describes the plasma membrane as a two-dimensional fluid of phospholipids in which proteins are embedded like mosaic tiles. 'Fluid' refers to the ability of lipids and many proteins to diffuse laterally within the leaflet; 'mosaic' describes the patchwork of proteins dotting the surface. Membrane fluidity depends on temperature, fatty acid tail saturation, and cholesterol content. Unsaturated hydrocarbon tails with kinked double bonds prevent tight packing and increase fluidity, while saturated tails pack tightly and decrease fluidity. The membrane is asymmetric: the composition of the outer and inner leaflets differs, which is critical for signaling and membrane trafficking.

Phospholipids, Cholesterol, and Membrane Proteins

Phospholipids are amphipathic molecules with a hydrophilic phosphate head and two hydrophobic fatty acid tails. In aqueous solution, they spontaneously form a bilayer — heads facing outward toward water, tails tucked inside away from water. Cholesterol, a sterol lipid, intercalates between phospholipids and acts as a fluidity buffer: at high temperatures it restrains movement (reducing fluidity), while at low temperatures it prevents tight packing (maintaining fluidity). Membrane proteins fall into two classes. Integral proteins are embedded within the hydrophobic core of the bilayer; many are transmembrane proteins that span the entire membrane. Peripheral proteins are associated with the membrane surface via electrostatic interactions or lipid anchors — they do not penetrate the hydrophobic core. Membrane proteins serve as channels, carriers, pumps, receptors, adhesion molecules, and enzymes.

Passive Transport, Osmosis, and Tonicity

Passive transport moves solutes down their electrochemical gradient without energy expenditure. Simple diffusion occurs when small, nonpolar molecules (O₂, CO₂) or very small polar molecules (water, urea) slip directly through the bilayer. This process does not require a protein and proceeds until equilibrium is reached. Osmosis is the diffusion of water across a semipermeable membrane toward the compartment with higher solute concentration. Tonicity describes the effect of extracellular solutions on cell volume: isotonic (equal solute concentration; no net water movement; cell volume stable), hypotonic (lower external solute concentration; water enters the cell causing swelling and potential lysis), and hypertonic (higher external solute concentration; water leaves the cell causing crenation). The MCAT will often ask you to predict water movement given osmolarity values — remember that water always moves to dilute the more concentrated side.

Facilitated Diffusion

Facilitated diffusion also moves solutes down their concentration gradient without energy, but it requires a transmembrane protein. Channel proteins form aqueous pores selective for specific ions or small molecules (e.g., aquaporins for water, ion channels for Na⁺, K⁺, Ca²⁺). Carrier proteins (transporters) bind their solute and undergo a conformational change to shuttle it across. A key example is the GLUT family of glucose transporters. Facilitated diffusion exhibits saturation kinetics — at high solute concentrations, transport rate plateaus because all protein binding sites are occupied (Vmax behavior, analogous to enzyme kinetics).

Primary and Secondary Active Transport

Primary active transport uses energy directly from ATP hydrolysis to move solutes against their electrochemical gradient. The classic example is the Na⁺/K⁺ ATPase, which pumps 3 Na⁺ out and 2 K⁺ in per ATP hydrolyzed, establishing concentration gradients essential for secondary transport and membrane potential. Other examples include the Ca²⁺ ATPase (SERCA pump) in the sarcoplasmic reticulum and the H⁺/K⁺ ATPase in the stomach. Secondary active transport (cotransport) harnesses the potential energy stored in an ion gradient — typically the Na⁺ gradient established by the Na⁺/K⁺ pump. In symport, the driving ion and the transported solute move in the same direction (e.g., Na⁺/glucose symporter SGLT1 in the intestinal epithelium). In antiport, they move in opposite directions (e.g., Na⁺/Ca²⁺ exchanger). Critically, secondary active transport is indirectly ATP-dependent: it depends on the gradient maintained by the primary pump.

Endocytosis and Exocytosis

Large molecules and particles cross the membrane via vesicle-mediated transport. Endocytosis brings material into the cell by invagination of the plasma membrane, forming a vesicle. Subtypes include phagocytosis (cell 'eating' — engulfment of large particles), pinocytosis (cell 'drinking' — uptake of extracellular fluid), and receptor-mediated endocytosis (specific ligand binding to receptors concentrated in clathrin-coated pits, e.g., LDL uptake). Exocytosis exports material by fusing intracellular vesicles with the plasma membrane, releasing their contents into the extracellular space. This is how neurotransmitters are released at synapses, how hormones are secreted, and how membrane proteins and lipids are delivered to the cell surface. Both processes require ATP and are mediated by SNARE proteins and other fusion machinery.

Membrane Potential

The membrane potential (Vm) is the electrical potential difference across the plasma membrane, arising from the unequal distribution of ions and the selective permeability of the membrane. In most cells at rest, the interior is negative relative to the exterior (typically −40 to −90 mV). The resting membrane potential is dominated by K⁺ leak channels, which allow K⁺ to flow out down its concentration gradient, leaving behind negative charges. The Nernst equation calculates the equilibrium potential for a single ion: E_ion = (RT/zF) × ln([ion]_out / [ion]_in). At physiological temperature (37°C), this simplifies to approximately E_ion = (61.5/z) × log([ion]_out / [ion]_in). The Goldman-Hodgkin-Katz equation accounts for multiple permeant ions. On the MCAT, you will most commonly apply the Nernst equation to predict the direction of ion flow given concentration gradients.

How it works

The plasma membrane achieves selective permeability through two parallel mechanisms: the phospholipid bilayer itself blocks large polar and charged solutes, while specific transport proteins provide regulated pathways for everything the cell needs. Consider how a neuron fires: the Na⁺/K⁺ ATPase maintains steep Na⁺ and K⁺ gradients (primary active transport). Voltage-gated Na⁺ channels open upon depolarization, allowing Na⁺ to rush in by facilitated diffusion. The resulting action potential triggers voltage-gated Ca²⁺ channels to open; Ca²⁺ influx drives neurotransmitter-containing vesicles to fuse with the membrane (exocytosis). Meanwhile, the Na⁺ gradient powers secondary active transport of neurotransmitters back into the presynaptic terminal (reuptake). Every step ties back to membrane transport fundamentals. The Nernst potential logic explains why ions flow the way they do: if Vm is more negative than E_ion, positive ions flow inward; if Vm is more positive, they flow outward.

How it works

The plasma membrane achieves selective permeability through two parallel mechanisms: the phospholipid bilayer itself blocks large polar and charged solutes, while specific transport proteins provide regulated pathways for everything the cell needs. Consider how a neuron fires: the Na⁺/K⁺ ATPase maintains steep Na⁺ and K⁺ gradients (primary active transport). Voltage-gated Na⁺ channels open upon depolarization, allowing Na⁺ to rush in by facilitated diffusion. The resulting action potential triggers voltage-gated Ca²⁺ channels to open; Ca²⁺ influx drives neurotransmitter-containing vesicles to fuse with the membrane (exocytosis). Meanwhile, the Na⁺ gradient powers secondary active transport of neurotransmitters back into the presynaptic terminal (reuptake). Every step ties back to membrane transport fundamentals. The Nernst potential logic explains why ions flow the way they do: if Vm is more negative than E_ion, positive ions flow inward; if Vm is more positive, they flow outward.

Comparisons

• Biochemistry: Membrane lipid composition and protein structure determine function. The amphipathic nature of phospholipids explains spontaneous bilayer formation — a core thermodynamics and intermolecular forces concept.
• Physiology: The Na⁺/K⁺ pump and ion gradients are foundational for renal reabsorption (SGLT2 in the proximal tubule), cardiac action potentials (Ca²⁺ handling), and epithelial transport throughout the body.
• Neuroscience: Resting membrane potential, action potentials, synaptic transmission, and neurotransmitter reuptake all depend on the transport mechanisms described here.
• Pharmacology: Many drugs target membrane proteins — SSRIs block serotonin reuptake transporters, loop diuretics inhibit the Na⁺/K⁺/2Cl⁻ cotransporter, and local anesthetics block voltage-gated Na⁺ channels.

Common confusions

• Passive vs. active transport confusion: Facilitated diffusion does NOT use ATP — it is passive. Students often conflate 'requires a protein' with 'requires energy.' A carrier protein moving solute down its gradient is passive.
• Osmolarity vs. tonicity: Osmolarity counts all solute particles per liter. Tonicity considers only non-penetrating solutes. A solution can be iso-osmolar but hypotonic if the solute is permeant (e.g., urea).
• Primary vs. secondary active transport: If the question mentions ATP directly powering the pump, it is primary. If it mentions using a Na⁺ or H⁺ gradient, it is secondary — even though ATP was originally used to create that gradient.
• Nernst sign errors: For K⁺ (~5 mM out, ~140 mM in), E_K is roughly −90 mV. For Na⁺ (~145 mM out, ~12 mM in), E_Na is roughly +65 mV. The sign matters: positive ions flow toward negative potentials.
• Cholesterol's dual role: Cholesterol can increase or decrease fluidity depending on temperature. At body temperature, it generally decreases fluidity; at low temperatures, it prevents membranes from becoming too rigid.
• Aquaporins: Water can cross the membrane slowly by simple diffusion, but physiologically relevant water flux requires aquaporin channels (facilitated diffusion). The MCAT tests this distinction explicitly.

Quick review

• Fluid mosaic model: phospholipid bilayer + embedded proteins; lateral diffusion; asymmetric leaflets.
• Cholesterol buffers membrane fluidity — decreases at high temp, increases at low temp.
• Passive transport = down gradient, no ATP; active transport = against gradient, ATP (or ion gradient) required.
• Osmosis: water moves toward higher solute concentration; tonicity depends on non-penetrating solutes.
• Na⁺/K⁺ ATPase: 3 Na⁺ out, 2 K⁺ in per ATP — electrogenic, establishes gradients for secondary transport.
• Nernst equation: E_K ≈ −90 mV, E_Na ≈ +65 mV at typical mammalian concentrations.
• Endocytosis: phagocytosis (particles), pinocytosis (fluid), receptor-mediated (specific ligands via clathrin).
• Exocytosis: constitutive (continuous) vs. regulated (Ca²⁺-triggered, e.g., neurotransmitter release).
• Saturation kinetics: carrier-mediated transport has Vmax — binding sites become limiting.
• Membrane potential is closest to the equilibrium potential of the most permeable ion (usually K⁺ at rest).