🔬Biophysics Unit 7 – Transport Mechanisms Across Membranes
Cell membranes are dynamic structures that regulate the flow of molecules and ions. They consist of a phospholipid bilayer with embedded proteins, cholesterol, and glycolipids, forming a fluid mosaic that allows lateral diffusion and maintains asymmetry.
Transport across membranes occurs through passive and active mechanisms. Passive transport includes diffusion and osmosis, while active transport uses energy to move molecules against concentration gradients. Understanding these processes is crucial for cell biology and medicine.
Membranes consist of a phospholipid bilayer with hydrophilic heads facing outward and hydrophobic tails facing inward
Proteins embedded in the membrane serve various functions such as transport, signaling, and structural support (integral proteins)
Cholesterol molecules interspersed in the membrane regulate fluidity and stability
Glycolipids and glycoproteins on the extracellular side of the membrane participate in cell recognition and adhesion
Glycolipids have sugar moieties attached to the lipid head group
Glycoproteins have sugar moieties attached to the protein component
The fluid mosaic model describes the dynamic nature of the membrane, allowing lateral diffusion of lipids and proteins
Membrane asymmetry refers to the different composition of the inner and outer leaflets of the bilayer, which is maintained by specific enzymes (flippases and floppases)
Types of Transport Mechanisms
Transport mechanisms enable the movement of molecules and ions across the membrane
Passive transport occurs down the concentration gradient without requiring energy input (diffusion and osmosis)
Facilitated diffusion involves the use of carrier proteins or channels to transport specific molecules down their concentration gradient
Active transport moves molecules against their concentration gradient using energy from ATP hydrolysis or electrochemical gradients
Primary active transport directly uses ATP (sodium-potassium pump)
Secondary active transport couples the movement of one molecule against its gradient with the movement of another down its gradient (sodium-glucose cotransporter)
Endocytosis and exocytosis are bulk transport mechanisms that involve the formation of vesicles to transport large molecules or particles
Endocytosis brings substances into the cell (phagocytosis and pinocytosis)
Exocytosis releases substances from the cell (neurotransmitter release)
Passive Transport: Diffusion and Osmosis
Diffusion is the net movement of molecules from a region of high concentration to a region of low concentration
Fick's law describes the rate of diffusion, which depends on the concentration gradient, diffusion coefficient, and membrane permeability
Simple diffusion occurs through the lipid bilayer for small, nonpolar molecules (oxygen and carbon dioxide)
Osmosis is the diffusion of water across a semipermeable membrane driven by a concentration gradient of solutes
Water moves from a region of low solute concentration (high water potential) to a region of high solute concentration (low water potential)
Tonicity describes the effect of extracellular solute concentration on cell volume
Isotonic solutions have equal solute concentrations inside and outside the cell, maintaining cell volume
Hypotonic solutions have lower solute concentrations outside the cell, causing water influx and cell swelling
Hypertonic solutions have higher solute concentrations outside the cell, causing water efflux and cell shrinkage
Facilitated Diffusion and Carrier Proteins
Facilitated diffusion involves the use of carrier proteins or channels to transport specific molecules down their concentration gradient
Carrier proteins undergo conformational changes to bind and release the transported molecule (glucose transporters)
The binding site is alternately exposed to the extracellular and intracellular sides of the membrane
Channels form hydrophilic pores that allow the passage of specific ions or small molecules (potassium channels)
Facilitated diffusion exhibits saturation kinetics, as the rate of transport reaches a maximum when all carrier proteins or channels are occupied
Specificity is achieved through the complementary shape and charge of the binding site and the transported molecule
Facilitated diffusion is inhibited by competitive inhibitors that bind to the same site as the transported molecule
Active Transport and ATP-Driven Processes
Active transport moves molecules against their concentration gradient using energy from ATP hydrolysis or electrochemical gradients
Primary active transport directly uses ATP to drive the transport process
The sodium-potassium pump (Na+/K+ ATPase) maintains the low intracellular Na+ and high intracellular K+ concentrations
The calcium pump (Ca2+ ATPase) removes Ca2+ from the cytoplasm, maintaining low intracellular Ca2+ levels
Secondary active transport couples the movement of one molecule against its gradient with the movement of another down its gradient
The sodium-glucose cotransporter (SGLT) uses the Na+ gradient to transport glucose into the cell
The sodium-calcium exchanger (NCX) uses the Na+ gradient to remove Ca2+ from the cell
ATP-binding cassette (ABC) transporters use ATP hydrolysis to pump various substances out of the cell (multidrug resistance protein)
V-type ATPases pump protons into organelles (lysosomes and vacuoles) to maintain acidic pH
Ion Channels and Electrical Signaling
Ion channels are integral membrane proteins that form pores to allow the passage of specific ions
Gating mechanisms regulate the opening and closing of ion channels in response to stimuli
Voltage-gated channels open or close in response to changes in membrane potential (sodium and potassium channels in neurons)
Ligand-gated channels open or close in response to the binding of specific molecules (nicotinic acetylcholine receptor)
Mechanosensitive channels open or close in response to mechanical stimuli (hair cells in the inner ear)
The selective permeability of ion channels is determined by the size and charge of the pore (selectivity filter)
The concerted action of ion channels underlies electrical signaling in excitable cells (neurons and muscle cells)
The action potential is generated by the sequential opening of sodium and potassium channels
Synaptic transmission involves the release of neurotransmitters that bind to ligand-gated channels on the postsynaptic cell
Membrane Potential and Electrochemical Gradients
The membrane potential is the electrical potential difference across the membrane, with the intracellular side typically negative relative to the extracellular side
The resting membrane potential is determined by the unequal distribution of ions across the membrane and the selective permeability of ion channels
The potassium equilibrium potential (EK) is the major determinant of the resting potential due to the high permeability of potassium channels
The Nernst equation relates the equilibrium potential of an ion to its concentration gradient across the membrane
Eion=zFRTln[ion]in[ion]out
The Goldman-Hodgkin-Katz equation calculates the membrane potential based on the permeabilities and concentrations of multiple ions
Electrochemical gradients combine the effects of concentration gradients and electrical potentials to drive ion movement across the membrane
Applications in Cell Biology and Medicine
Understanding transport mechanisms is crucial for explaining various cellular processes and diseases
Ion channels are targets for many drugs, such as local anesthetics (sodium channel blockers) and antiepileptic drugs (GABA receptor agonists)
Mutations in ion channels can lead to channelopathies, such as cystic fibrosis (CFTR chloride channel) and long QT syndrome (potassium channel)
Active transport is essential for maintaining cellular homeostasis and proper functioning of organs
The sodium-potassium pump is critical for the function of neurons, muscle cells, and epithelial cells
The calcium pump is important for muscle contraction and neurotransmitter release
Facilitated diffusion is exploited by cancer cells to increase glucose uptake (GLUT1 overexpression)
Osmosis and tonicity are relevant in clinical settings, such as the use of intravenous fluids and the treatment of cerebral edema
Membrane potential and electrochemical gradients are the basis for electrophysiological techniques used in research and diagnosis (patch-clamp and electroencephalography)