Cell Physiology/Part 1/1.1 Membrane Structure

1.1 Membrane Structure

The Fluid Mosaic Model and Molecular Architecture of Biological Membranes

🎯 Learning Objectives

  • β€’Describe the structure and organization of the phospholipid bilayer
  • β€’Explain the fluid mosaic model of membrane structure
  • β€’Classify membrane proteins by their association with the bilayer
  • β€’Understand how cholesterol modulates membrane fluidity

πŸ”¬The Lipid Bilayer

The cell membrane is composed of a phospholipid bilayer approximately 7-8 nm thick. This structure forms spontaneously due to the amphipathic nature of phospholipidsβ€”molecules with both hydrophilic (water-loving) and hydrophobic (water-fearing) regions.

Phospholipid Structure

  • β†’Hydrophilic Head: Phosphate group + glycerol backbone, faces aqueous environment
  • β†’Hydrophobic Tails: Two fatty acid chains (16-18 carbons), face membrane interior
  • β†’Saturated tails: Straight chains, pack tightly, decrease fluidity
  • β†’Unsaturated tails: Kinked chains (cis double bonds), increase fluidity

Major Phospholipid Classes

  • β†’Phosphatidylcholine (PC): Most abundant, outer leaflet
  • β†’Phosphatidylethanolamine (PE): Inner leaflet, cone-shaped
  • β†’Phosphatidylserine (PS): Inner leaflet, negative charge, apoptosis marker
  • β†’Sphingomyelin: Outer leaflet, lipid rafts, signaling

πŸ“Š Membrane Asymmetry

The two leaflets of the bilayer have different lipid compositionsβ€”a phenomenon called membrane asymmetry. This asymmetry is actively maintained by enzymes called flippases, floppases, and scramblases.

Outer Leaflet

  • β€’ Phosphatidylcholine (PC)
  • β€’ Sphingomyelin
  • β€’ Glycolipids

Inner Leaflet

  • β€’ Phosphatidylethanolamine (PE)
  • β€’ Phosphatidylserine (PS)
  • β€’ Phosphatidylinositol (PI)

🌊The Fluid Mosaic Model

Proposed by Singer and Nicolson in 1972, the fluid mosaic model describes the membrane as a two-dimensional liquid in which proteins "float" within a sea of lipids. The term "mosaic" refers to the pattern of proteins embedded in the lipid bilayer.

πŸ”„

Lateral Diffusion

Lipids move sideways: D β‰ˆ 10⁻⁸ cmΒ²/s

↕️

Flip-Flop

Rare without enzymes: t₁/β‚‚ ~ hours to days

πŸ”€

Rotation

Lipids spin around their axis: very fast

🌑️ Factors Affecting Membrane Fluidity

Increase Fluidity ↑

  • βœ“Higher temperature
  • βœ“More unsaturated fatty acids
  • βœ“Shorter fatty acid chains
  • βœ“Lower cholesterol (at low T)

Decrease Fluidity ↓

  • βœ—Lower temperature
  • βœ—More saturated fatty acids
  • βœ—Longer fatty acid chains
  • βœ—Higher cholesterol (at high T)

🧬Membrane Proteins

Proteins constitute approximately 50% of membrane mass and are responsible for most membrane functions including transport, signaling, and adhesion.

Integral (Intrinsic) Proteins

Embedded within the lipid bilayer; require detergents for extraction.

  • Transmembrane proteins: Span the entire membrane
  • Single-pass: Cross once (e.g., growth factor receptors)
  • Multi-pass: Cross multiple times (e.g., GPCRs, ion channels)
  • Ξ±-helix or Ξ²-barrel: Common transmembrane structures

Peripheral (Extrinsic) Proteins

Attached to membrane surface; easily extracted with salt solutions.

  • Electrostatic: Ionic bonds to lipid heads
  • Protein-protein: Bound to integral proteins
  • Examples: Spectrin, ankyrin, cytochrome c
  • Functions: Cytoskeleton attachment, signaling

Lipid-Anchored Proteins

GPI Anchors

Glycosylphosphatidylinositol; outer leaflet; e.g., alkaline phosphatase

Prenyl Groups

Farnesyl or geranylgeranyl; inner leaflet; e.g., Ras proteins

Fatty Acyl

Myristoyl or palmitoyl; inner leaflet; e.g., Src kinase

⭐Cholesterol: The Fluidity Buffer

Cholesterol comprises ~25% of membrane lipids in animal cells and acts as a "fluidity buffer," moderating membrane properties across temperature ranges.

At High Temperature

Cholesterol restricts phospholipid movement, decreasing fluidity and preventing the membrane from becoming too fluid.

At Low Temperature

Cholesterol prevents tight packing of phospholipids, increasing fluidity and preventing the membrane from solidifying.

Lipid Rafts

Cholesterol-rich microdomains that are more ordered and tightly packed. These "rafts" concentrate specific proteins involved in signaling (e.g., GPI-anchored proteins, caveolins).

πŸ“ Key Parameters

Membrane Thickness
d β‰ˆ 7-8 nm
Lipid Lateral Diffusion
D β‰ˆ 10⁻⁸ cmΒ²/s
Cholesterol Content
~25% of membrane lipids
Protein Content
~50% of membrane mass

πŸ₯ Clinical Relevance

Hereditary Spherocytosis

Defects in spectrin/ankyrin cause RBC membrane instability and hemolytic anemia

Paroxysmal Nocturnal Hemoglobinuria

GPI anchor deficiency leads to complement-mediated RBC lysis

Atherosclerosis

Excess cholesterol accumulation in arterial walls

Cancer Metastasis

Altered membrane composition enables cell migration

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