🔬Biophysics Unit 7 – Transport Mechanisms Across Membranes

Membrane Structure and Properties

• 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
  • $E_{ion} = \frac{RT}{zF} \ln \frac{[ion]_{out}}{[ion]_{in}}$
• The Goldman-Hodgkin-Katz equation calculates the membrane potential based on the permeabilities and concentrations of multiple ions
  • $V_m = \frac{RT}{F} \ln \frac{P_K[K^+]_{out} + P_{Na}[Na^+]_{out} + P_{Cl}[Cl^-]_{in}}{P_K[K^+]_{in} + P_{Na}[Na^+]_{in} + P_{Cl}[Cl^-]_{out}}$
• 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)