The Cell Membrane
Spec mapping: AQA 7402 Section 3.2.3 — cell membrane structure (refer to the official AQA specification document for exact wording).
The cell surface membrane (plasma membrane) is the boundary that defines the cell as a discrete entity. Every transaction between a cell and its environment — every nutrient absorbed, every signal received, every waste product expelled, every immune recognition event — depends on this single phospholipid bilayer and the proteins embedded within it. At A-Level you are expected to know the fluid mosaic model to undergraduate-bordering depth: not only the named components but why each is present, what would happen if it were absent, and how membrane composition is tuned across cell types and temperatures.
Key Definition: The fluid mosaic model (proposed by S. Jonathan Singer and Garth Nicolson, 1972) describes the cell membrane as a fluid phospholipid bilayer (in which phospholipids move laterally within their leaflet) with a mosaic of proteins floating in and through it. The model superseded earlier static sandwich models of membrane architecture and remains the consensus framework today.
The Phospholipid Bilayer
Structure of a Phospholipid
A phospholipid consists of:
- A glycerol molecule.
- Two fatty acid chains (the hydrophobic 'tails'). These can be saturated (no C=C double bonds, straight chains) or unsaturated (one or more C=C double bonds, causing kinks in the chains).
- A phosphate group (the hydrophilic 'head'), which may have additional groups attached (e.g., choline in phosphatidylcholine).
This gives the phospholipid an amphipathic nature — one end is hydrophilic (water-loving) and the other is hydrophobic (water-repelling).
Bilayer Arrangement
In an aqueous environment, phospholipids spontaneously arrange into a bilayer:
- The hydrophilic phosphate heads face outward towards the aqueous environment on both sides (extracellular fluid and cytoplasm).
- The hydrophobic fatty acid tails face inward, away from water, forming a hydrophobic core.
- This arrangement is thermodynamically stable and self-assembling — it forms spontaneously when phospholipids are placed in water.
Properties of the Bilayer
- Fluid: individual phospholipid molecules can move laterally within their layer (lateral diffusion), rotate on their axes, and flex their fatty acid tails. This gives the membrane flexibility. However, flip-flop (movement from one layer to the other) is rare without the help of enzymes called flippases.
- Selectively permeable: the hydrophobic core allows small, non-polar molecules (e.g., O₂, CO₂, steroid hormones) to pass through by diffusion. It is impermeable to large molecules, polar molecules, and ions, which require transport proteins.
Membrane Proteins
Proteins make up approximately 25–75% of membrane mass (depending on the cell type) and perform a wide range of functions.
Intrinsic (Integral) Proteins
- Span the entire membrane (transmembrane proteins) or are deeply embedded in one leaflet.
- Held in place by hydrophobic interactions between their non-polar amino acid R-groups and the hydrophobic tails of the phospholipids.
- Examples include:
- Channel proteins — provide hydrophilic pores that allow specific ions or polar molecules to pass through by facilitated diffusion. Many are gated (opened or closed by specific signals, e.g., voltage-gated sodium channels in neurones).
- Carrier proteins — bind to specific molecules and undergo a conformational change to transport them across the membrane. Involved in both facilitated diffusion and active transport.
- Receptor proteins — have a specific binding site on the extracellular surface for signalling molecules (ligands) such as hormones or neurotransmitters. Binding triggers a response inside the cell (signal transduction).
Extrinsic (Peripheral) Proteins
- Found on the surface of the membrane (either inner or outer face).
- Not embedded in the hydrophobic core; attached by ionic bonds or hydrogen bonds to intrinsic proteins or to the phospholipid heads.
- Functions include acting as enzymes, anchoring proteins (connecting the membrane to the cytoskeleton), and components of cell signalling pathways.
Glycoproteins and Glycolipids
- Glycoproteins — proteins with short carbohydrate (oligosaccharide) chains attached, found on the extracellular surface of the membrane.
- Glycolipids — lipids with short carbohydrate chains attached, also on the extracellular surface.
Together, glycoproteins and glycolipids form the glycocalyx (cell coat), which:
- Acts as cell recognition markers (antigens) — allows cells to identify self from non-self (essential for the immune system).
- Provides cell-cell adhesion — helps cells stick together to form tissues.
- Plays a role in cell signalling — acts as receptor sites for hormones and other chemical signals.
- Provides protection — a physical barrier against mechanical damage and chemical attack.
Exam Tip: The ABO blood group system is an example of glycolipid/glycoprotein variation. Different glycolipid antigens (A, B, or neither) on the surface of red blood cells determine blood type.
Cholesterol
Cholesterol is a small, hydrophobic molecule that sits between the phospholipid tails in the membrane of animal cells (plant cells have related molecules called phytosterols).
Effects on Membrane Properties
| Temperature | Effect of Cholesterol |
|---|
| High temperatures | Cholesterol reduces membrane fluidity by restricting the movement of phospholipids, preventing the membrane from becoming too fluid and permeable |
| Low temperatures | Cholesterol prevents the phospholipids from packing too closely together and crystallising, maintaining membrane fluidity |
In summary, cholesterol acts as a fluidity buffer, stabilising the membrane across a range of temperatures. It also:
- Increases the mechanical stability of the membrane.
- Reduces the permeability of the membrane to small water-soluble molecules and ions.
- Does not make the membrane completely rigid — it allows controlled flexibility.
Factors Affecting Membrane Permeability
The permeability of cell membranes can be affected by several factors. A common practical investigation involves placing beetroot tissue in solutions at different temperatures or in different concentrations of alcohol and measuring the leakage of the red pigment betacyanin using a colorimeter.
Temperature
- Below optimum (below approximately 0 °C): phospholipids have little kinetic energy. The membrane becomes rigid and may crack or develop gaps, increasing permeability.
- 0–40 °C: the membrane functions normally. Slight increases in temperature increase the kinetic energy of phospholipids, causing slightly increased permeability.
- Above approximately 40 °C: the phospholipid bilayer becomes increasingly fluid. Proteins begin to denature (vibrations break hydrogen bonds and other weak bonds maintaining tertiary/quaternary structure). Channel and carrier proteins lose their specific shape, and the membrane loses its selective permeability. Betacyanin leaks freely from beetroot cells.
Solvents (e.g., Ethanol)
- Organic solvents dissolve the phospholipids in the membrane, disrupting its structure.
- Higher concentrations of ethanol cause greater disruption, increasing membrane permeability (more betacyanin leaks out of beetroot cells).
pH
- Extreme pH values (very acidic or very alkaline) can denature membrane proteins, disrupting transport and increasing permeability.
- Changes in pH can also alter the charge on phospholipid heads, affecting the bilayer structure.
Lipid Composition and Membrane Asymmetry
Cell membranes are not chemically uniform. Several layers of complexity are worth knowing at A-Level depth.
Asymmetry between leaflets
The two leaflets of the bilayer have markedly different lipid compositions. In the human red blood cell, phosphatidylcholine and sphingomyelin are concentrated in the outer leaflet, while phosphatidylserine and phosphatidylethanolamine are concentrated in the inner leaflet. Asymmetry is maintained by ATP-dependent transporters:
- Flippases move specific lipids from the outer to the inner leaflet.
- Floppases move lipids in the opposite direction.
- Scramblases randomise lipid distribution during specific events (e.g., apoptosis externalises phosphatidylserine, marking dying cells for clearance by phagocytes — the "eat me" signal).
Lipid rafts
Within the bilayer plane, lipids are not uniformly mixed. Lipid rafts are cholesterol- and sphingolipid-rich microdomains that float in a sea of more fluid phosphatidylcholine. Rafts concentrate certain signalling proteins (e.g., GPI-anchored proteins, some receptor tyrosine kinases), facilitating organised signal transduction.
Saturation and fluidity
Phospholipids with saturated fatty acids pack tightly because their straight tails fit together, producing low fluidity. Phospholipids with unsaturated fatty acids have cis double bonds that introduce kinks, preventing close packing and producing higher fluidity. Cells in cold environments (Arctic fish, plants exposed to frost) adjust the proportion of unsaturated lipids upward, preserving membrane fluidity at low temperature. This is homeoviscous adaptation and is a recurring evolutionary theme.
Membrane Proteins — Mobility and Anchoring
Not every protein in the membrane drifts freely. Several mechanisms restrict lateral mobility:
- Cytoskeletal tethering. Proteins like spectrin in red blood cells form a flexible meshwork beneath the membrane, anchored to integral proteins (band 3) and restricting their motion.
- Lipid raft confinement. Proteins partitioned into rafts cannot freely exchange with non-raft regions.
- Tight junctions in epithelial cells block lateral diffusion of proteins between apical and basolateral domains, allowing functional polarisation.
The classic experiment demonstrating membrane fluidity was the Frye–Edidin mouse–human cell fusion (1970): fluorescent antibodies against mouse and human membrane proteins were initially segregated on the fused heterokaryon's surface, but within minutes had mixed completely, demonstrating that membrane proteins are mobile in the plane of the bilayer.
Investigating Membrane Permeability — The Beetroot Practical
This is a required practical for AQA A-Level Biology.
Method
- Cut equal-sized cylinders of beetroot using a cork borer. Wash thoroughly in distilled water to remove pigment from damaged cells.
- Place cylinders in water baths at a range of temperatures (e.g., 20, 30, 40, 50, 60, 70 °C) for a set time (e.g., 30 minutes).
- Remove the beetroot pieces and measure the absorbance (or percentage transmission) of the surrounding solution using a colorimeter with a blue-green filter (wavelength ~530 nm).
- Higher absorbance (or lower transmission) indicates more betacyanin has leaked out, meaning greater membrane damage.
Expected Results
- Little leakage up to ~40 °C.
- Rapid increase in leakage above ~40 °C as proteins denature and the bilayer becomes disrupted.
- Maximum leakage at the highest temperatures tested.
Exam Tip: In this practical, control variables include the size and mass of beetroot pieces, the volume of water, the time in the water bath, and the type of beetroot. The independent variable is temperature; the dependent variable is absorbance (a measure of pigment release).
Cell Signalling and the Cell Membrane
Many cell-signalling pathways depend on membrane receptors:
- A signalling molecule (e.g., a hormone such as insulin) binds to a specific receptor protein on the cell surface membrane.
- This triggers a cascade of intracellular events (signal transduction), often involving second messengers such as cyclic AMP (cAMP).
- The specificity of cell signalling depends on the complementary shape of the receptor and ligand — only target cells with the correct receptor respond to a given signal.
Membrane-bound receptors allow the cell to respond to water-soluble signalling molecules that cannot cross the hydrophobic bilayer. Lipid-soluble signals (e.g., steroid hormones) can diffuse through the membrane and bind to intracellular receptors directly.
Receptor Classes
- G-protein-coupled receptors (GPCRs) — seven-transmembrane-helix proteins that activate intracellular G proteins on ligand binding. The largest receptor superfamily; targets include adrenaline (β-adrenergic receptors), light (rhodopsin in rod cells), and many drug targets.
- Receptor tyrosine kinases (RTKs) — single transmembrane proteins that dimerise and autophosphorylate on ligand binding. Targets include insulin, EGF (epidermal growth factor — bound by HER2 receptors, the target of trastuzumab in HER2+ breast cancer covered in lesson 9).
- Ion-channel-coupled receptors — ligand-gated ion channels, e.g., the nicotinic acetylcholine receptor at the neuromuscular junction.
- Intracellular receptors — for lipid-soluble signals that cross the membrane. Steroid hormone receptors (oestrogen, testosterone, cortisol, vitamin D) bind their ligand in the cytoplasm or nucleus and then act directly as transcription factors.
The diversity of receptor types reflects the diversity of signals cells must respond to. The membrane is therefore not just a barrier but an information-processing interface.
Cell-Cell Junctions
Beyond the cell surface membrane proper, animal cells use specialised structures to interact with neighbours and the extracellular matrix. These are not in the AQA core spec but provide context.
- Tight junctions (zonula occludens) seal adjacent epithelial cells together, blocking paracellular fluid movement and segregating apical from basolateral membrane domains. The leaky tight junctions in the gut allow water but not solutes; the watertight tight junctions in the urinary bladder allow concentrated urine to be retained.
- Adherens junctions anchor adjacent cells via cadherin proteins linked to the actin cytoskeleton. Critical for tissue integrity.
- Desmosomes are spot-weld junctions linking intermediate filaments of adjacent cells, providing mechanical strength to tissues subject to stretching (skin, heart muscle).
- Gap junctions are protein channels connecting the cytoplasm of adjacent cells, allowing small molecules and ions to flow between them. Critical in cardiac muscle (synchronising contraction) and in early embryogenesis.
Plant cells have plasmodesmata — cytoplasmic channels through cell walls that connect adjacent cells. They allow movement of small molecules between cells and constitute the symplast pathway of water and solute transport, an alternative to the apoplast pathway.
Comparing Membrane Components Across Cell Types
The composition of the cell surface membrane varies considerably across cell types, tuned to physiological role.
- Red blood cells. Lack a nucleus; membrane reinforced by an underlying spectrin–actin cytoskeleton via ankyrin and band 3. Contains many glycoproteins (ABO antigens). Lacks cholesterol-rich raft domains found in other cell types.
- Myelin sheaths. Wrapped around axons; lipid-rich (~75% lipid, 25% protein) to insulate the axon for fast saltatory conduction. The high lipid content makes myelin appear white in tissue, hence "white matter".
- Mitochondrial inner membrane. Protein-rich (~75% protein, 25% lipid) because it carries the electron transport chain complexes and ATP synthase. Cardiolipin, a four-tailed phospholipid, is enriched here and contributes to the cristae's tight curvature.
- Synaptic vesicle membrane. Specialised for rapid fusion; enriched in v-SNAREs (synaptobrevin), synaptotagmin (Ca²⁺ sensor) and ATP-driven proton pumps for neurotransmitter loading.
These examples illustrate that "the membrane" is not a single biochemical entity but a tunable structure adapted to context.
Drugs That Target the Membrane
A substantial fraction of pharmaceuticals target membrane components — illustrating the membrane's central role in physiology.