-Study Notes on Membrane Transport & Cell Surface Receptors

Membrane Structure: The Fluid Mosaic Model

  • Components of Cell Membrane:

    • Phospholipid Bilayer: Amphipathic molecules with hydrophilic (polar) heads and hydrophobic (nonpolar) fatty acid tails.

    • Cholesterol: Regulates membrane fluidity and stability across varying temperatures.

    • Carbohydrates: Glycoproteins and glycolipids forming the glycocalyx, essential for cell-cell recognition.

    • Integral (Transmembrane) Proteins: Span the entire bilayer; act as transporters, receptors, or enzymes.

    • Peripheral Proteins: Attached to surfaces; involved in signaling or maintaining the cytoskeleton.

Function of Membrane Proteins

  • Key Functions:

    • Transport: Moving ions and polar molecules across the membrane.

    • Signal Transduction: Relaying extracellular messages to the cell interior.

    • Cell Recognition: Identification tags for the immune system.

    • Intercellular Joining: Forming junctions between adjacent cells.

Selective Permeability of Membranes

  • The lipid bilayer is a semi-permeable barrier:

    • Permeable: Small, nonpolar, uncharged molecules (e.g., O2, CO2, N2).

    • Slightly Permeable: Small, uncharged polar molecules like water (H2O).

    • Impermeable: Ions (Na*+, K+, Cl−*, Ca2+) and large polar molecules (glucose) require transport proteins.

Concentration Gradients and Electrochemical Potentials

  • Chemical Gradient: The difference in solute concentration between the cytosol and extracellular fluid.

  • Electrical Gradient (Membrane Potential): The difference in electrical charge across the membrane.

  • Electrochemical Gradient: The combined influence of concentration and electrical gradients on ion movement.

  • Ion Concentrations (typical values):

    • Sodium (Na+*)*: Higher extracellularly (145 mM) vs intracellularly (5-15 mM).

    • Potassium (K+*)*: Higher intracellularly (140 mM) vs extracellularly (5 mM).

    • Calcium (Ca2+): Extremely low intracellularly (10−4 mM) vs extracellularly (1-2 mM).

    • Chloride (Cl−): Higher extracellularly (110 mM) vs intracellularly (5-15 mM).

Transport Mechanisms Overview

  • Passive Transport: Movement down concentration gradient (no energy required). Includes simple diffusion and facilitated diffusion.

  • Active Transport: Movement against gradient (requires energy from ATP or ion gradients).

Diffusion and Osmosis

  • Simple Diffusion: Random thermal motion leads to net movement until equilibrium.

  • Factors Affecting Diffusion Rate:

    • Steepness of Gradient: Greater difference leads to faster diffusion.

    • Temperature: Higher temperature increases speed.

    • Mass of Molecule: Smaller molecules diffuse faster.

    • Surface Area: Larger area increases transport capacity.

    • Diffusion Distance: Thinner membranes allow faster exchange.

  • Osmosis: The diffusion of water through a selectively permeable membrane. Water moves toward higher solute concentration.

Facilitated Diffusion (Carrier-Mediated Passive Transport)

  • Used for polar or charged molecules (glucose, amino acids).

  • Mechanism: Solute binds to carrier protein, inducing conformational change.

  • Saturation: Limited by number of available carriers (Vmax).

Ion Channels

  • Pores that allow specific ions to pass through by diffusion.

  • Gating Mechanisms:

    • Voltage-gated: Open in response to membrane potential changes.

    • Ligand-gated: Open when a chemical binds to the receptor.

    • Mechanically-gated: Open in response to physical deformation.

Active Transport Mechanisms

  1. Primary Active Transport: Energy from ATP hydrolysis.

    • Na+/K+ ATPase (Sodium-Potassium Pump)**: Pumps 3 Na*+* out and 2 K*+* in per ATP. Maintains resting membrane potential and cell volume.

  2. Secondary Active Transport (Cotransport): Uses energy from electrochemical gradients.

    • Symporters: Move two substances in the same direction (e.g., Sodium-Glucose symporter).

    • Antiporters: Move substances in opposite directions (e.g., Na*+/H+* exchanger).

Cell Surface Receptors and Signaling

  • Signal Transduction: Process by which an extracellular signal is converted into a cellular response.

  • Three Major Classes of Receptors:

    1. Ion-Channel-Coupled Receptors: Rapidly convert chemical signals into electrical signals by changing ion permeability.

    2. G-Protein-Coupled Receptors (GPCRs):

      • Seven transmembrane domains (7-TM receptors).

      • Activate trimeric G-protein (Gα, Gβ, Gγ).

      • Gα subunit exchanges GDP for GTP and modulates enzymes like Adenylyl Cyclase (producing cAMP).

    3. Enzyme-Coupled Receptors:

      • Receptor Tyrosine Kinases (RTKs): Ligand binding causes dimerization and autophosphorylation, creating docking sites for signaling proteins (e.g., Ras protein triggering MAP-kinase cascade).

Clinical Significance

  • Defects in membrane transport lead to diseases like Cystic Fibrosis (defective Cl− channels).

  • GPCRs are targets of approximately 30-50% of all modern medicinal drugs.