The Fluid Mosaic Model of Membrane Structure

Every living cell is bounded by a plasma (cell surface) membrane, and eukaryotic cells contain many internal membranes surrounding organelles such as mitochondria, chloroplasts, the nucleus, endoplasmic reticulum and Golgi apparatus. These membranes are not inert barriers — they are highly organised, dynamic structures that control what enters and leaves compartments, host enzymes, and carry out cell signalling. This lesson covers OCR A-Level Biology A specification point 2.1.5 (a) — the roles of cell membranes and (b) — the fluid mosaic model of membrane structure and the roles of its components.

A firm grasp of membrane architecture underpins every subsequent lesson in this course: diffusion, osmosis, active transport, signalling and even how cells coordinate mitosis depend on what the membrane is and does.

1. Roles of Cell Membranes

Biological membranes perform a remarkable range of functions:

Compartmentalisation — separating the cell from its surroundings and creating specialised internal environments inside organelles.
Selective permeability — allowing some substances to cross while excluding others.
Cell signalling — receiving chemical signals (hormones, neurotransmitters) via receptor proteins.
Cell recognition — using glycoproteins and glycolipids as identification markers (the ABO blood group antigens are a classic example).
Site of biochemical reactions — the inner mitochondrial membrane houses the electron transport chain; thylakoid membranes carry photosystems.
Cell–cell adhesion — tight junctions, desmosomes and plasmodesmata in plants.
Maintenance of cell shape — together with the cytoskeleton.

Key Definition — Partially Permeable Membrane: A membrane that allows certain small, uncharged or lipid-soluble molecules to pass freely while restricting the passage of larger, charged or hydrophilic molecules.

2. Historical Context — From Davson–Danielli to Singer–Nicolson

Our current picture of membrane structure — the fluid mosaic model — was proposed by S. Jonathan Singer and Garth Nicolson in 1972. It replaced earlier models, most notably the Davson–Danielli "sandwich" model (1935), which placed protein layers on the outside of a lipid bilayer like bread around a filling.

Why was the Davson–Danielli model rejected?

Freeze-fracture electron microscopy split membranes through the middle of the bilayer and revealed proteins embedded in and passing through the lipid, not sitting only on the surface.
Flourescent labelling experiments by Frye and Edidin (1970) showed that membrane proteins move laterally within the bilayer — membranes are fluid, not static.
Different membranes have very different protein:lipid ratios, which a uniform sandwich could not explain.

The fluid mosaic model describes the membrane as:

Fluid — phospholipids and most proteins can move laterally within the plane of the bilayer.
Mosaic — proteins of varied size, shape and function are scattered throughout the bilayer, like tiles in a mosaic.

graph TD
  A[Cell Membrane - Singer-Nicolson 1972] --> B[Phospholipid Bilayer]
  A --> C[Proteins - intrinsic and extrinsic]
  A --> D[Cholesterol]
  A --> E[Glycoproteins and Glycolipids]
  B --> B1[Hydrophilic phosphate heads<br/>face aqueous environment]
  B --> B2[Hydrophobic fatty acid tails<br/>face each other]

3. The Phospholipid Bilayer

The structural backbone of every biological membrane is a phospholipid bilayer — two layers of phospholipid molecules arranged tail-to-tail.

3.1 Phospholipid Structure

A phospholipid consists of:

A glycerol backbone.
Two fatty acid chains esterified to the first and second carbons (the hydrophobic "tails").
A phosphate group esterified to the third carbon, often linked to a small polar molecule such as choline (forming phosphatidylcholine). This is the hydrophilic "head".

Because the molecule has both a hydrophilic head and hydrophobic tails, it is amphipathic (or amphiphilic).

3.2 Why a Bilayer?

In aqueous surroundings, phospholipids spontaneously arrange themselves so that:

Hydrophilic heads face outward, interacting with water inside and outside the cell.
Hydrophobic tails face inward, away from water, held together by hydrophobic interactions and van der Waals forces.

This self-assembly is driven by the thermodynamics of water exclusion (the hydrophobic effect) and produces a stable, 7–10 nm thick bilayer.

Region	Molecule type	Character
Head	Phosphate + glycerol + polar group	Hydrophilic
Tails	Two fatty acid chains	Hydrophobic

Exam Tip: Always describe phospholipids as amphipathic or having both hydrophilic and hydrophobic regions — not simply as "polar".

3.3 Consequences for Permeability

The hydrophobic core of the bilayer is the fundamental reason that:

Small non-polar molecules (O₂, CO₂, N₂, steroid hormones) can dissolve in and cross the membrane freely.
Small polar uncharged molecules (H₂O, urea) cross slowly by simple diffusion — though water also uses protein channels called aquaporins.
Ions (Na⁺, K⁺, Ca²⁺, Cl⁻) and large polar molecules (glucose, amino acids) cannot cross unaided — they require transport proteins.

4. Membrane Proteins

Proteins make up 25–75% of the mass of a membrane depending on its role (the inner mitochondrial membrane is protein-rich; the myelin sheath is lipid-rich). They are classified by how tightly they are held in the membrane.

4.1 Intrinsic (Integral) Proteins

Intrinsic proteins are embedded within the phospholipid bilayer. Their surfaces that contact the hydrophobic tails have hydrophobic amino acid R-groups (e.g. valine, leucine, phenylalanine), while regions exposed to the aqueous environment are hydrophilic.

Transmembrane proteins span the entire bilayer. These include:

Channel proteins — form hydrophilic pores for specific ions or molecules.
Carrier proteins — bind a specific substrate and change shape to move it across.
Pumps — carrier proteins that use ATP to move substances against a concentration gradient (e.g. the Na⁺/K⁺ ATPase).
Receptor proteins — bind signalling molecules on the outside and transmit a signal inside.
Enzymes — e.g. ATP synthase in the inner mitochondrial membrane.

4.2 Extrinsic (Peripheral) Proteins

Extrinsic proteins sit on the surface of the membrane (inner or outer leaflet) and associate with it via weak non-covalent interactions with phospholipid heads or intrinsic proteins. Many act as part of signalling cascades or the cytoskeletal attachment network.

Feature	Intrinsic (integral)	Extrinsic (peripheral)
Location	Embedded in bilayer	On surface of bilayer
Amino acid character	Hydrophobic regions in core	Hydrophilic throughout
Removal	Detergents that disrupt bilayer	Mild salt or pH change
Typical roles	Channels, carriers, receptors, enzymes	Signalling, cytoskeletal attachment

5. Cholesterol — The Membrane Modulator

Cholesterol is a small, lipid-based molecule (a steroid with four fused rings) found in most animal cell membranes. It sits between phospholipids, with its polar hydroxyl group near the phosphate heads and its hydrophobic rings nestled against the fatty acid tails.

Functions of cholesterol:

Reduces fluidity at high temperatures by restricting phospholipid movement.
Prevents the membrane becoming too rigid at low temperatures by stopping the fatty acid tails packing too closely.
Reduces permeability to small water-soluble ions and molecules by filling gaps between phospholipids.
Increases mechanical stability — mammalian membranes without cholesterol are fragile.

Plants do not contain cholesterol but have related molecules called phytosterols (such as stigmasterol). Prokaryotes generally lack sterols.

Exam Tip: Cholesterol is often described as a "fluidity buffer". It decreases fluidity when it would otherwise be too high, and increases it (by preventing crystallisation) when it would otherwise be too low.

6. Glycoproteins and Glycolipids

Some membrane lipids and proteins carry short carbohydrate (oligosaccharide) chains. These chains extend from the outer (extracellular) surface of the plasma membrane only.

Glycoproteins — protein with covalently attached carbohydrate.
Glycolipids — lipid (usually a phospholipid) with covalently attached carbohydrate.

Together they form the glycocalyx, a carbohydrate-rich "coat" on the outside of the cell.

Functions include:

Cell recognition and identification — the ABO blood group antigens are glycoproteins/glycolipids on red blood cell membranes.
Cell adhesion — binding cells together to form tissues.
Receptors for signalling molecules (e.g. hormones and neurotransmitters).
Receptors for infection — viruses and toxins often recognise specific cell-surface glycoproteins (e.g. influenza binds sialic acid).
Stabilising the membrane by forming hydrogen bonds with water molecules around the cell.

7. Fluidity of the Membrane

The "fluid" part of the fluid mosaic model is real and important. Phospholipids in each leaflet diffuse laterally roughly 10⁷ times per second, while flip-flop (transverse) movement across the bilayer is extremely rare because the polar heads cannot easily pass through the hydrophobic core.

Factors affecting fluidity:

Factor	Effect on fluidity
Increasing temperature	Increases — more kinetic energy, tails move more
Unsaturated fatty acids (double bonds, "kinks")	Increase — kinks prevent tight packing
Saturated fatty acids (straight)	Decrease — pack tightly
Cholesterol at high T	Decrease — restrains movement
Cholesterol at low T	Increase — prevents crystallisation
Longer fatty acid tails	Decrease — more van der Waals contact

Organisms in cold environments (e.g. Arctic fish, cold-tolerant plants) have membranes with a higher proportion of unsaturated fatty acids to keep the membrane fluid at low temperature — a phenomenon called homeoviscous adaptation.

8. Common Exam Mistakes

Describing the membrane as a "sandwich" of proteins — this is the outdated Davson–Danielli model, not the fluid mosaic model.
Saying carbohydrate chains are on both sides of the plasma membrane. They are on the outer (extracellular) surface only.
Calling every transmembrane protein a "channel". Channels form pores; carriers change shape; pumps use ATP — all are different.
Forgetting that cholesterol is an animal component — plant cells contain phytosterols instead.
Describing phospholipids as "polar" — they are amphipathic, with both polar and non-polar regions.
Claiming that ions can pass through the phospholipid bilayer directly. They cannot — they need channel or carrier proteins.
Writing that membranes are "fully permeable" or "impermeable". They are partially (selectively) permeable.

9. Exam-Style Questions

Describe the roles of cholesterol in the plasma membrane of an animal cell. (3)
Explain why a phospholipid forms a bilayer in an aqueous environment. (4)
Distinguish between intrinsic and extrinsic membrane proteins. (3)
Explain why the fluid mosaic model replaced the Davson–Danielli model. (4)

Model answer for (2): "Phospholipids are amphipathic: they have hydrophilic phosphate heads and hydrophobic fatty acid tails. In an aqueous environment the hydrophilic heads interact with water while the hydrophobic tails are excluded from water. The most thermodynamically stable arrangement is a bilayer, with heads facing outward into the aqueous environments on both sides and tails shielded from water in the interior. This arrangement is stabilised by hydrophobic interactions and van der Waals forces between tails."

Summary

The fluid mosaic model (Singer and Nicolson, 1972) describes membranes as a fluid phospholipid bilayer studded with a mosaic of proteins.
Phospholipids form the bilayer; they are amphipathic with hydrophilic heads and hydrophobic tails.
Intrinsic proteins span or are embedded in the bilayer (channels, carriers, pumps, receptors, enzymes); extrinsic proteins sit on the surface.
Cholesterol is a fluidity buffer — it restricts movement at high temperatures and prevents rigidity at low temperatures.
Glycoproteins and glycolipids on the outer surface form the glycocalyx and act in cell recognition, adhesion and signalling.
The membrane is partially permeable: small non-polar molecules cross freely, while ions and large polar molecules need transport proteins.
Fluidity depends on temperature, fatty acid saturation, chain length and cholesterol content.

Lesson 1: The Fluid Mosaic Model of Membrane Structure