Membranes: Structure and Transport

5.1 The Structure of Membranes

  • Basic membrane structure
    • Phospholipids are arranged in a bilayer: hydrophilic (polar) heads face outward toward water, hydrophobic (nonpolar) tails face the interior of the membrane.
  • Fluid Mosaic Model (Singer & Nicolson, 1972)
    • The membrane is a dynamic, fluid lipid bilayer with a mosaic of proteins embedded in or associated with it.
    • Integral proteins: embedded in the membrane; have hydrophobic regions that span the bilayer.
    • Peripheral proteins: on the surface; have polar or charged regions.
    • Membrane-associated proteins: not part of the membrane itself but interact with it.
  • Five components of cellular membranes (overview)
    1. Phospholipid bilayer – flexible matrix; barrier to permeability.
    2. Sterols – nonpolar molecules with a hydroxyl (-OH) group.
    3. Integral membrane proteins – embedded in the phospholipid bilayer; can move within the membrane; some have hydrophobic transmembrane domains (TMDs).
    4. Interior protein network – provides structural support and shape; includes peripheral and membrane-associated proteins.
    5. Cell-surface markers – glycoproteins and glycolipids added to the membrane by the ER; act as cell identity markers.
  • Studying membranes – imaging techniques
    • Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) are used to study membranes.
    • Freeze-fracture microscopy visualizes the inside of the membrane by fracturing a frozen sample and preparing a replica for electron microscopy.
  • Practical context
    • Understanding membrane structure underpins how membranes control permeability, signaling, and transport of substances.

5.2 Phospholipids: The Membrane’s Foundation

  • Three lipid classes (≈1000 distinct cellular lipids)
    1. Glycerol phospholipids – head groups can be zwitterionic or anionic.
    2. Sphingolipids – contain saturated hydrocarbon chains; important for vertebrate nervous system.
    3. Sterols – cholesterol is the primary sterol in animals; nonpolar aside from the hydroxyl group.
  • Phospholipid structure (example: phosphatidylcholine)
    • Phospholipids are amphipathic: polar heads are hydrophilic; nonpolar tails are hydrophobic.
    • Glycerol backbone with two fatty acid tails and a phosphate-containing head group.
  • Spontaneous bilayer formation
    • Due to amphipathic nature, phospholipids spontaneously form bilayers with polar heads outward and tails inward.
  • Phospholipid bilayer properties
    • Bilayers are fluid; lipids and unanchored proteins can diffuse laterally within the membrane.
    • Hydrogen bonding among water and polar heads helps hold layers together.
  • Membrane domains and thickness
    • Transmembrane domain (TMD) length varies by membrane type:
    • ER membrane: typically shorter TMDs (≈20 amino acids); more fluid and thinner; unsaturated lipids predominate; little cholesterol.
    • Plasma membrane (PM): longer TMDs (≈25 amino acids); mix of saturated and unsaturated lipids with cholesterol; less fluid and thicker.
  • Factors influencing membrane fluidity
    • Fluidity decreases with:
    • Saturated and mono cis-unsaturated fatty acids.
    • Longer fatty acid tails.
    • Lower temperatures.
    • Bacteria modify fluidity at low temperatures by desaturating fatty acids (adding double bonds).
  • Lipid composition across membranes
    • ER membrane: mainly unsaturated lipids; little cholesterol; higher fluidity; thinner with shorter TMDs.
    • PM: mix of saturated/unsaturated lipids and cholesterol; lower fluidity; thicker with longer TMDs.
  • Terminology and structure-function context
    • Anionic head groups and cytosolic orientation influence interactions with proteins and cytoskeleton.
    • The distinct lipid compositions contribute to membrane curvature, thickness, and microdomain formation.

5.3 Proteins: Multifunctional Components

  • Major functions of membrane proteins
    1. Transporters – move substances across the membrane.
    2. Enzymes – catalyze reactions at the membrane surface or within the bilayer.
    3. Cell-surface receptors – detect and transduce chemical signals.
    4. Cell-surface identity markers – mark cell type and status.
    5. Cell-to-cell adhesion proteins – mediate direct cell–cell interactions.
    6. Attachments to the cytoskeleton – connect membrane to cytoskeleton for shape and mechanics.
    7. Affect membrane structure – contribute to membrane curvature and organization.
  • Protein topology and organization
    • Transmembrane proteins span the lipid bilayer; have nonpolar regions embedded in the bilayer and polar regions protruding on both sides.
    • Domains include α-helical segments or β-pleated sheet segments forming transmembrane spans.
    • A single transmembrane domain can anchor a protein; many proteins have multiple transmembrane domains.
  • Transmembrane domains and receptors
    • Transmembrane domains are often hydrophobic α-helices.
    • Some receptors are classified by the number of transmembrane domains they possess.
  • Pores and channels
    • Proteins with extensive nonpolar regions can form pores, such as β-barrel structures, where the interior is polar and allows water and small polar molecules to cross.
  • Anchoring molecules
    • Anchoring molecules attach membrane proteins to the membrane surface via modified lipids.
    • Characteristics: nonpolar regions insert into the bilayer; contain domains that covalently bond to proteins.
  • Structure–function relationship
    • The diversity of membrane protein structures underpins their wide range of functions.

5.4 Passive Transport Across Membranes

  • Core idea
    • Passive transport moves molecules without energy input, driven by concentration gradients.
    • Diffusion: movement from high to low concentration; continues until equilibrium is reached.
  • Barriers to diffusion
    • The hydrophobic interior of the membrane is the major barrier;
    • Nonpolar molecules cross readily.
    • Small polar molecules cross with limited permeability.
    • Larger polar molecules and ions have very limited permeability.
  • Facilitated diffusion – selectivity through proteins
    • Channel proteins – hydrophilic channels that open/close (gated channels).
    • Carrier proteins – bind specific molecules and undergo conformational changes to shuttle the molecule across; rate can saturate due to transporter availability.
  • Channel proteins and ion flow
    • Ion channels allow ions to cross the nonpolar interior by providing a hydrophilic passage.
    • Gated channels respond to stimuli (chemical or electrical).
    • Direction depends on:
    • Relative concentrations on each side of the membrane.
    • Voltage differences across the membrane.
    • Whether the channel is open or closed (gated state).
  • Facilitated diffusion by carriers
    • Carrier proteins enable movement of ions or solutes (e.g., sugars, amino acids) along their concentration gradient via diffusion.
    • Transport is saturable due to finite transporter numbers.
  • Osmosis – diffusion of water
    • Cytoplasm is an aqueous solution; water is the solvent; solutes are dissolved substances.
    • Osmosis is the net diffusion of water across a semipermeable membrane toward higher solute concentration.
    • Aquaporins – specialized water channels that facilitate osmosis.
  • Osmotic concentration and tonicity
    • Hypertonic: higher solute concentration outside than inside.
    • Hypotonic: lower solute concentration outside than inside.
    • Isotonic: equal osmotic concentration across the membrane.
  • Osmotic pressure and consequences
    • Osmotic pressure is the pressure required to stop osmosis; can cause cell swelling in hypotonic solutions if unchecked.
    • Plant cells use turgor pressure to maintain rigidity; prokaryotes and fungi may be protected by cell walls; animal cells require isotonic surroundings to avoid lysis.

5.5 Active Transport Across Membranes

  • Key concept
    • Active transport requires energy (ATP directly or indirectly) to move substances against their concentration gradient, using selective carrier proteins.
  • Carrier proteins in active transport
    • Uniporters – move one molecule at a time.
    • Symporters – move two molecules in the same direction.
    • Antiporters – move two molecules in opposite directions.
    • Note: terms can also describe facilitated diffusion carriers (context-dependent).
  • Sodium–Potassium Pump (Na+/K+ ATPase)
    • Direct use of ATP to move ions against their gradients via an antiporter.
    • Typical cycle (illustrated in the membrane protein mechanism):
      1) ATP and 3 Na+ ions bind to the pump.
      2) ATP is hydrolyzed to phosphorylate the pump.
      3) Phosphorylation causes a conformational change, reducing affinity for Na+ and releasing Na+ to the extracellular space.
      4) The pump assumes a conformation with higher affinity for K+; extracellular K+ binds.
      5) Dephosphorylation triggers return to the original conformation; K+ is released inside.
      6) The pump returns to its initial conformation; ATP can bind again to restart the cycle.
    • Stoichiometry: for each cycle, 3 Na+ ions are pumped out and 2 K+ ions are pumped in, powered by 1 molecule of ATP.
  • Coupled (secondary) transport
    • Uses energy released by the diffusion of one molecule to power the transport of another molecule against its gradient.
    • Can be a symporter (same direction) or an antiporter (opposite directions).
    • Example: Glucose–Na+ symport, which harnesses Na+ diffusion energy to move glucose against its gradient.
  • Conceptual summary
    • Active transport enables cells to concentrate essential solutes, maintain membrane potentials, and power secondary transport processes.

5.6 Bulk Transport by Endocytosis and Exocytosis

  • Endocytosis – bringing materials into the cell
    • Requires energy.
    • Types:
    • Phagocytosis – uptake of particulate matter (e.g., bacteria).
    • Pinocytosis – uptake of fluids and dissolved solutes.
    • Receptor-mediated endocytosis – selective uptake of molecules after binding to specific receptors; involves clathrin-coated pits.
  • Exocytosis – releasing materials from the cell
    • Requires energy.
    • Roles include secretion of hormones, neurotransmitters, digestive enzymes; export of cell wall materials in plants.
  • Receptor-mediated endocytosis – disease example
    • Familial hypercholesterolemia: LDL receptors lack tails and fail to localize to clathrin-coated pits, preventing vesicle formation; cholesterol remains in the bloodstream and accumulates as arterial plaques, increasing heart attack risk.
  • Integrative context
    • Bulk transport complements selective transport by allowing cells to intake or expel large quantities of material as needed for signaling, nutrition, and remodeling.

Key equations and concepts (summary)

  • Diffusion (Fick's first law): J=−DdCdxJ = -D \frac{dC}{dx}
    • J: flux, rate of diffusion; D: diffusion coefficient; dC/dx: concentration gradient.
  • Osmosis and osmotic pressure (Van’t Hoff-like relation for ideal solutions): π=iCRT\pi = i C R T
    • \pi: osmotic pressure; i: van 't Hoff factor (number of particles into which solute dissociates); C: molar concentration; R: gas constant; T: absolute temperature.
  • Na+/K+ ATPase stoichiometry (active transport):
    • Per ATP hydrolyzed: 3 Na+ exported and 2 K+ imported (against gradients).
  • Conceptual notes
    • The membrane is a selectively permeable barrier shaped by lipid composition and protein content.
    • Fluidity is modulated by lipid saturation, tail length, temperature, and cholesterol presence.
    • Carriers and channels provide selective permeability, enabling rapid yet controlled transport across the membrane.
    • Endocytosis and exocytosis enable bulk movement for signaling and material exchange, with receptor-mediated endocytosis providing specificity and ties to human disease (e.g., familial hypercholesterolemia).