Cytology Lecture 2: Cell Membrane

1. What Is the Cell Membrane?

• Defines the external boundary of every cell - no membrane means no cell
• Extremely thin (just two molecular layers), flexible, and self-sealing
• Described by the fluid mosaic model: individual lipid and protein molecules move freely in the plane of the membrane, forming a constantly changing mosaic pattern

2. Functions of the Cell Membrane

1. Cell communication - surface receptors receive signals from outside
2. Transport - channels and transporters import/export small molecules
3. Structural flexibility - allows cell growth, movement, and shape changes

3. Components

Lipids

• Membranes are made of a lipid bilayer + proteins
• Lipids are amphipathic: hydrophilic (phosphate + alcohol) head + hydrophobic (fatty acid) tail
• Most abundant lipids are phospholipids (glycerophospholipids)
• Saturated vs. unsaturated fatty acid chains affect membrane shape and fluidity

Lipid Bilayer

• Self-assembles in aqueous environments (energetically favorable)
• Impermeable to most water-soluble molecules
• Molecules can move laterally within one leaflet (frequent) but flip-flop between leaflets is rare
• Most membranes are asymmetric - inner and outer leaflets differ
• Scramblase ensures even distribution of newly made phospholipids

Cholesterol

• Makes up ~20% of animal cell membrane lipids
• Modulates fluidity - diffuses between saturated and unsaturated phospholipids
• Acts as a fluidity buffer across different temperatures

Fluidity Factors

• Longer fatty acid chains = less fluid
• More saturated chains = less fluid

4. Membrane Proteins

• Make up ~50% of the mass of the plasma membrane
• Types by topology:
  • Integral (transmembrane) proteins: monotopic, bitopic, or polytopic
  • Peripheral proteins: associate via electrostatic/hydrogen-bond interactions
• Key functional roles:
  • Transporters & channels - move nutrients, ions, metabolites
  • Anchors - link membrane to macromolecules
  • Receptors - detect and relay signals
  • Enzymes - catalyze reactions
• Lipid rafts: rigid microdomains of clustered proteins and lipids involved in signal transduction

5. Membrane Carbohydrates

• Glycoproteins: proteins with short oligosaccharide chains
• Proteoglycans: proteins with long polysaccharide chains
• Glycolipids: lipids with covalently attached sugars
• Glycocalyx: carbohydrate-rich layer on the cell surface - functions in protection, cell-cell recognition, signaling, adhesion, and acting as a barrier to pathogens
• Clinical example: ABO blood groups determined by glycolipid differences

6. Cell Cortex

• A meshwork of filamentous proteins attached to the inner face of the plasma membrane
• Stabilizes the membrane structure of animal cells
• In red blood cells, spectrin is the main cortex protein, giving RBCs their distinctive biconcave shape
• Spectrin is connected to the membrane via intracellular attachment proteins linked to specific transmembrane proteins

7. Selective Permeability

• Small nonpolar molecules (O₂, CO₂) diffuse freely across the membrane
• Small uncharged polar molecules (H₂O, ethanol) also diffuse readily
• Large uncharged polar molecules (glucose) cross with great difficulty
• Charged molecules / inorganic ions (Na⁺, K⁺) are essentially impermeant
• The bilayer is ~1 billion times more permeable to H₂O than to ions

8. Transport Mechanisms

Passive Transport

• Movement down a concentration gradient - no energy required
• Channels: selective pores, discriminate by size and charge (e.g., ion channels)
• Transporters/carriers: bind specific molecules (e.g., glucose transporter - 12 isoforms encoded in the human genome)

Active Transport (Pumps)

1. Gradient-driven pumps - couple uphill transport of one solute to downhill transport of another
2. ATP-driven pumps - use ATP hydrolysis (e.g., Na⁺/K⁺-ATPase, keeps cytosolic Na⁺ 10-30x lower and K⁺ 10-30x higher than extracellular fluid)
3. Light-driven pumps - use sunlight energy

Osmosis & Aquaporins

• Aquaporins facilitate water flow across the membrane
• Water moves from low to high solute concentration (osmosis)
• Animal cells maintain osmotic balance by expelling solutes (e.g., via Na⁺ pumps)

9. ABC Transporters

• Large family of ATP-binding cassette pumps; conserved from bacteria to humans
• Examples:
  • CFTR - exports Cl⁻; mutations cause cystic fibrosis
  • MRPs (Multidrug Resistance Proteins) - efflux drugs from cells, contributing to drug resistance in cancer
  • E. coli has 80 ABC transporter genes (2% of its genome); linked to antibiotic resistance and bacterial virulence

10. Vesicular Transport (Endocytosis)

• Pinocytosis ("cell drinking"): ingestion of fluid and molecules via small vesicles (<150 nm)
• Phagocytosis ("cell eating"): ingestion of large particles (>250 nm) such as bacteria and cell debris, forming phagosomes
• Receptor-mediated endocytosis: internalization of a ligand after it binds a specific receptor

11. Membrane Fusion

• Membranes can fuse with other membranes without losing continuity
• Steps: recognition → close apposition → outer leaflet disruption (hemifusion) → complete bilayer fusion
• Regulated fusion requires a specific signal
• SNARE proteins and SNAP25 mediate fusion
• Botulinum toxin (Clostridium botulinum) is a protease that cleaves SNARE proteins, blocking neurotransmission and causing paralysis

Next Lecture Preview

• Seminar on cellular structures: organelles and the cytoskeleton

MCQ Questions - Cell Membrane

• A) A rigid structure with fixed proteins embedded in a static lipid layer
• B) A flexible lipid bilayer with freely moving proteins and lipids
• C) A single lipid layer with proteins attached only to the outer surface
• D) A carbohydrate-rich layer surrounding a protein core

• A) Cholesterol
• B) Glycolipids
• C) Phospholipids (glycerophospholipids)
• D) Proteoglycans

• A) Polar
• B) Amphipathic
• C) Nonpolar
• D) Ionic

• A) Shorter fatty acid chains
• B) More unsaturated fatty acids
• C) Higher cholesterol concentration at high temperature
• D) Longer, more saturated fatty acid chains

• A) 10%
• B) 25%
• C) 50%
• D) 75%

• A) It forms the backbone of the lipid bilayer
• B) It links membrane proteins to the cytoskeleton
• C) It modulates membrane fluidity by buffering changes at different temperatures
• D) It acts as a receptor for extracellular signals

• A) Peripheral protein
• B) Monotopic protein
• C) Bitopic protein
• D) Polytopic protein

• A) Glucose
• B) Na⁺ ions
• C) O₂ and CO₂
• D) Amino acids

• A) Phospholipids and cholesterol
• B) Glycoproteins, glycolipids, and proteoglycans
• C) Spectrin and actin filaments
• D) Integral membrane proteins

• A) Actin
• B) Tubulin
• C) Spectrin
• D) Clathrin

• A) Movement of molecules against their concentration gradient using ATP
• B) Spontaneous movement of molecules from high to low concentration without energy input
• C) Transport of ions using light energy
• D) Movement of molecules via vesicle formation

• A) Glucose
• B) Na⁺ and K⁺ ions
• C) Water molecules
• D) Amino acids

• A) High Na⁺ inside the cell and high K⁺ outside
• B) Low Na⁺ inside the cell and high K⁺ inside the cell
• C) Equal concentrations of Na⁺ and K⁺ on both sides
• D) High Cl⁻ inside and low Cl⁻ outside

• A) Na⁺
• B) K⁺
• C) Ca²⁺
• D) Cl⁻

• A) Ingestion of fluid via small vesicles (<150 nm)
• B) Ingestion of large particles such as bacteria (>250 nm)
• C) Receptor-binding and internalization of a hormone
• D) Fusion of secretory vesicles with the plasma membrane

• A) Light energy
• B) Concentration gradients
• C) ATP hydrolysis
• D) Electrochemical gradients

• A) Blocking acetylcholine receptors on muscle cells
• B) Cleaving SNARE proteins, preventing neurotransmitter release
• C) Disrupting the lipid bilayer of nerve cells
• D) Inhibiting Na⁺/K⁺-ATPase pumps

• A) Lateral diffusion
• B) Flip-flop
• C) Osmosis
• D) Endocytosis

• A) Areas where the bilayer is completely broken down
• B) Rigid specialized microdomains of clustered proteins and lipids involved in signal transduction
• C) Regions where cholesterol is completely absent
• D) Sites of vesicle formation during endocytosis

• A) 4
• B) 8
• C) 12
• D) 16