describe the roles of phospholipids, cholesterol, glycolipids, proteins and glycoproteins in cell surface membranes, with reference to stability, fluidity, permeability, transport (carrier proteins and channel proteins), cell signalling (cell surface

Fluid‑Mosaic Model – Definition

The cell surface membrane is a fluid‑mosaic structure.

It consists of a phospholipid bilayer into which cholesterol, glycolipids, integral (intrinsic) and peripheral (extrinsic) proteins, and glycoproteins are inter‑spersed.

The hydrophobic fatty‑acid tails face the interior of the bilayer, while the hydrophilic heads, protein domains and carbohydrate chains face the aqueous environments on either side of the membrane.

Key Structural Components (in syllabus order)

• Phospholipids
• Cholesterol
• Glycolipids
• Integral (intrinsic) proteins
• Peripheral (extrinsic) proteins
• Glycoproteins

1. Phospholipids

• Stability – Form the basic bilayer matrix; hydrophobic interactions between fatty‑acid tails hold the membrane together.
• Fluidity – Regulated by tail length and degree of unsaturation:

  • Unsaturated (kinked) tails ↑ fluidity.
  • Saturated tails ↓ fluidity.

• Permeability – Allows free diffusion of small non‑polar molecules (O₂, CO₂, lipid‑soluble hormones) but restricts ions and most polar solutes.
• Transport – Provides the lipid matrix in which carrier and channel proteins operate; “flip‑flop” of phospholipids is rare.
• Signalling / Recognition – Certain head‑group phospholipids (e.g., phosphatidylinositol) act as platforms for intracellular signalling cascades (e.g., PI‑3‑kinase pathway).

2. Cholesterol

• Stability – Inserts between phospholipids, filling gaps and preventing rupture under mechanical stress.
• Fluidity – Buffers fluidity:

  • At high temperature it restrains phospholipid movement (decreases fluidity).
  • At low temperature it prevents tight packing (increases fluidity).

• Permeability – Reduces passive diffusion of water‑soluble molecules by decreasing the size of transient gaps.
• Transport – Does not transport substances directly but creates a more ordered lipid environment that supports optimal protein function.
• Signalling / Recognition – Precursor for steroid hormones; can modulate the activity of membrane receptors and ion channels.

3. Glycolipids

• Stability – Contribute to membrane asymmetry and overall structural integrity.
• Fluidity – Bulky extracellular carbohydrate heads locally hinder lateral movement of neighbouring lipids, slightly reducing fluidity.
• Permeability – Little direct effect; their main role is external interaction.
• Transport – None.
• Signalling / Recognition – Carbohydrate chains act as cell‑surface antigens (e.g., blood‑group determinants) and are recognised by lectins, pathogens and immune cells.

4. Integral (Intrinsic) Proteins

• Stability – Anchor the membrane to the cytoskeleton or extracellular matrix, enhancing mechanical strength.
• Fluidity – Their presence creates local disturbances; a high protein concentration can lower overall membrane fluidity.
• Permeability – Form selective pores (channel proteins) that permit rapid passage of specific ions or water.
• Transport

  1. Channel proteins – Provide a continuous aqueous pathway; gated by voltage, ligands or mechanical forces.
  2. Carrier proteins – Undergo conformational changes to bind and move specific solutes (e.g., GLUT glucose transporter).
  3. Active transporters – Use ATP to move ions against a gradient (e.g., Na⁺/K⁺‑ATPase, linked to Topic 8 “Transport in mammals”).

• Signalling / Recognition

  • Receptors such as receptor‑tyrosine kinases (RTKs) and G‑protein‑coupled receptors (GPCRs) bind extracellular ligands and trigger intracellular cascades.
  • Extracellular domains can serve as antigens (relevant to Topic 11 “Immunity”).

5. Peripheral (Extrinsic) Proteins

• Stability – Link the membrane to the cytoskeleton, helping maintain cell shape and providing attachment sites for the extracellular matrix.
• Fluidity – Influence fluidity indirectly through interactions with integral proteins.
• Permeability – No direct effect.
• Transport – Often act as adaptor or scaffold proteins that assist carrier and channel complexes (e.g., ankyrin linking Na⁺ channels to the cytoskeleton).
• Signalling / Recognition

  • Transmit signals from membrane receptors to intracellular pathways (e.g., G‑protein α‑subunit, Src kinases).
  • Present antigenic peptides (MHC‑I) to immune cells – a direct link to the Immunology syllabus.

6. Glycoproteins

• Stability – Form part of the glycocalyx, protecting the membrane from mechanical damage and enzymatic attack.
• Fluidity – Extracellular carbohydrate chains are bulky and can impede the lateral diffusion of nearby lipids and proteins.
• Permeability – Indirect; they influence membrane organisation rather than forming pores.
• Transport – Frequently act as receptors that, upon ligand binding, initiate active transport processes (e.g., insulin receptor → GLUT4 translocation).
• Signalling / Recognition

  • Major receptors for hormones, growth factors and cytokines (e.g., insulin receptor, EGF receptor).
  • Carbohydrate moieties serve as cell‑surface antigens (blood groups, tissue‑type markers) – important for cell‑cell recognition and immunity.

Membrane Asymmetry & Lipid Rafts

• Asymmetry – The inner and outer leaflets contain different phospholipids (e.g., phosphatidylserine is mainly inner, sphingomyelin mainly outer). This asymmetry is essential for:

  • Signal transduction (inner‑leaflet phosphoinositides).
  • Apoptotic signalling (externalisation of phosphatidylserine).

• Lipid rafts – Cholesterol‑ and sphingolipid‑rich microdomains that float within the fluid membrane. They:

  • Concentrate certain receptors (e.g., GPI‑anchored proteins, some RTKs).
  • Facilitate rapid signal transduction and endocytosis.

Cell‑Signalling Pathway (Membrane‑Based)

1. Ligand secretion & transport – A signalling molecule (hormone, neurotransmitter, cytokine) is released by a source cell and travels through extracellular fluid to the target cell.
2. Receptor binding – The ligand binds to a specific membrane receptor (usually a glycoprotein). Typical receptor types in the syllabus:

   • G‑protein‑coupled receptors (GPCRs)
   • Receptor‑tyrosine kinases (RTKs)

3. Cellular response

   • Activation of intracellular second‑messenger systems (e.g., cAMP via adenylate cyclase, Ca²⁺ release from the endoplasmic reticulum).
   • Protein phosphorylation cascades, opening of ion channels, or activation of transcription factors.
   • Resulting physiological changes – altered enzyme activity, ion fluxes, gene expression, or active transport.

Quantitative Aspects (Optional but Useful for AO2/3)

• Membrane fluidity can be measured by fluorescence recovery after photobleaching (FRAP) or by the rate of lateral diffusion of labelled lipids.
• Permeability coefficients (P) are calculated from the rate of solute movement across a known membrane area and thickness.
• Cholesterol content is often expressed as a % of total membrane lipids; a typical mammalian plasma membrane contains ~30‑40 % cholesterol.

Clinical / Real‑World Relevance

• Atherosclerosis – Excess dietary cholesterol leads to plaque formation; membrane cholesterol is a key factor in disease development.
• Hereditary spherocytosis – Mutations in proteins that link the membrane to the cytoskeleton (e.g., ankyrin, spectrin) reduce stability, causing fragile, spherical erythrocytes.
• Cystic fibrosis – The CFTR protein is an ion channel; its malfunction illustrates the importance of integral membrane proteins for regulated transport.
• Pathogen entry – Many viruses and bacteria bind to specific glycolipids or glycoproteins (e.g., influenza HA to sialic‑acid‑containing glycolipids).

Summary Table – Membrane Components and Their Functions

Key Points for Revision (AO1–AO3)

1. Membrane fluidity results from a balance between phospholipid tail unsaturation and cholesterol content (buffering effect).
2. Selective permeability is achieved mainly by protein channels and carriers; the lipid bilayer blocks ions and most polar molecules.
3. Membrane‑based signalling follows the three‑stage sequence (ligand → receptor → intracellular response) and commonly uses second messengers such as cAMP and Ca²⁺.
4. Carbohydrate‑containing lipids and proteins provide the molecular basis for cell‑cell recognition, blood‑group antigens, and pathogen attachment.
5. Disruption of any membrane component (e.g., cholesterol depletion, altered phospholipid saturation, defective cytoskeletal links) can change stability, fluidity and function, leading to disease states such as atherosclerosis, hereditary spherocytosis or cystic fibrosis.
6. Remember the cross‑references:

   • Active transporters (Na⁺/K⁺‑ATPase) link to Topic 8 “Transport in mammals”.
   • MHC‑I and glycoprotein antigens link to Topic 11 “Immunity”.