Cell Transport Mechanisms: How Cells Move Molecules

Passive Transport

Passive transport moves substances across the membrane without the expenditure of cellular energy, relying instead on the natural tendency of molecules to move from regions of higher concentration to regions of lower concentration (down their concentration gradient). Simple diffusion is the most basic form: small, nonpolar molecules such as oxygen, carbon dioxide, and nitrogen gas dissolve directly in the lipid bilayer and pass through it freely. The rate of simple diffusion depends on the size of the concentration gradient, the temperature, and the lipid solubility of the molecule.

Facilitated diffusion uses membrane proteins to assist the transport of molecules that cannot easily cross the hydrophobic lipid bilayer on their own. Channel proteins form water-filled pores through which specific ions or small polar molecules can pass. Potassium leak channels, for example, allow potassium ions to flow out of the cell down their concentration gradient, contributing to the resting membrane potential of approximately -70 millivolts that characterizes most animal cells. Aquaporins are specialized channels that facilitate the rapid movement of water molecules, with each aquaporin channel capable of transporting up to 3 billion water molecules per second.

Carrier proteins bind specific substrates on one side of the membrane, undergo a conformational change, and release the substrate on the other side. The GLUT family of glucose transporters operates by facilitated diffusion, moving glucose down its concentration gradient from the blood (where glucose concentration is typically 5 millimolar) into cells (where glucose is quickly phosphorylated and thus kept at very low free concentration). Unlike channel proteins, carrier proteins are saturable: they have a maximum transport rate determined by the number of carrier molecules in the membrane and the speed of their conformational changes.

Osmosis is the net movement of water across a selectively permeable membrane from a region of lower solute concentration (higher water concentration) to a region of higher solute concentration (lower water concentration). The osmotic behavior of cells depends on the tonicity of the surrounding solution. In a hypotonic solution (lower solute concentration than the cell interior), water enters the cell, causing it to swell and potentially burst (lysis) in animal cells, though plant cells are protected from lysis by their rigid cell wall. In a hypertonic solution (higher solute concentration), water leaves the cell, causing it to shrink (crenation in animal cells, plasmolysis in plant cells). In an isotonic solution, there is no net water movement, and the cell maintains its normal volume.

Active Transport

Active transport uses energy, usually from ATP hydrolysis, to move substances against their concentration gradient, from regions of lower concentration to regions of higher concentration. This energy investment is essential for maintaining the concentration differences that drive passive transport, generate electrical signals in nerve and muscle cells, and allow cells to accumulate nutrients and expel waste.

Primary active transport directly couples ATP hydrolysis to the transport of specific ions or molecules. The sodium-potassium pump (Na+/K+-ATPase) is the most prominent example: for each molecule of ATP consumed, it exports three sodium ions and imports two potassium ions, creating and maintaining the steep concentration gradients of these ions across the membrane. This pump consumes roughly 25 percent of all the ATP produced by a resting cell and up to 70 percent in active neurons. The resulting sodium gradient is used to power many secondary transport processes, making the Na+/K+-ATPase the energetic foundation of a wide range of cellular activities.

The calcium ATPase (SERCA pump) in the endoplasmic reticulum membrane actively pumps calcium ions from the cytoplasm into the ER lumen, maintaining the 10,000-fold calcium concentration gradient that enables calcium signaling. The proton pump (H+/K+-ATPase) in the stomach lining secretes hydrochloric acid by pumping hydrogen ions into the stomach lumen against an enormous concentration gradient, achieving a final gastric pH of roughly 1 to 2.

Secondary active transport (cotransport) harnesses the energy stored in an ion concentration gradient, typically the sodium gradient created by the Na+/K+-ATPase, to drive the transport of another substance. In symport (cotransport), the ion and the transported substance move in the same direction. The sodium-glucose cotransporter (SGLT1) in the intestinal epithelium uses the inward flow of sodium ions down their concentration gradient to drive glucose absorption against its concentration gradient. In antiport (exchange), the ion and the transported substance move in opposite directions. The sodium-calcium exchanger (NCX) uses the sodium gradient to export calcium ions from the cell, an important mechanism for keeping cytoplasmic calcium levels low.

Bulk Transport

Bulk transport mechanisms move large molecules, particles, or large quantities of material across the membrane using membrane-bound vesicles. These processes require energy and involve dramatic remodeling of the plasma membrane.

Endocytosis brings material into the cell by engulfing it in a vesicle formed from the plasma membrane. Phagocytosis ("cell eating") is used by immune cells to engulf large particles such as bacteria, dead cells, and debris. The cell extends pseudopods around the particle, enclosing it in a large vesicle called a phagosome that fuses with lysosomes for digestion. Pinocytosis ("cell drinking") nonselectively internalizes small droplets of extracellular fluid along with whatever solutes they contain. Receptor-mediated endocytosis is the most selective form: specific molecules bind to surface receptors that cluster in clathrin-coated pits, which then invaginate to form clathrin-coated vesicles. This mechanism is used to import cholesterol (via LDL receptors), iron (via transferrin receptors), and many other specific molecules.

Exocytosis moves material out of the cell by fusing intracellular vesicles with the plasma membrane and releasing their contents to the exterior. Constitutive exocytosis occurs continuously and delivers newly synthesized membrane proteins and lipids to the cell surface. Regulated exocytosis stores material in secretory vesicles that fuse with the plasma membrane only in response to a specific signal. Neurotransmitter release at synapses is a precisely controlled form of regulated exocytosis: when an action potential reaches the nerve terminal, calcium influx triggers the fusion of synaptic vesicles with the presynaptic membrane, releasing neurotransmitter molecules into the synaptic cleft in less than a millisecond.

Intracellular Transport

Transport within the cell is equally important. Vesicular transport moves cargo between organelles of the endomembrane system (ER, Golgi, lysosomes) and between the Golgi and the plasma membrane. COPII-coated vesicles carry cargo from the ER to the Golgi, while COPI-coated vesicles retrieve escaped ER-resident proteins from the Golgi back to the ER. Clathrin-coated vesicles transport cargo from the Golgi to lysosomes and from the plasma membrane into the cell during endocytosis.

Motor protein-based transport moves organelles, vesicles, and other cargo along cytoskeletal tracks. Kinesin motors walk along microtubules toward the cell periphery (plus-end directed), while dynein motors move toward the cell center (minus-end directed). Myosin motors move cargo along actin filaments. In neurons, where the cell body may be a meter or more from the synaptic terminal, microtubule-based transport is essential for delivering synaptic vesicle precursors, mitochondria, and other components to the nerve terminal and for returning signaling molecules and recycled materials to the cell body.