Phospholipids and Cell Membranes

Every living cell is wrapped in a membrane only about 5 to 10 nanometres thick, thousands of times thinner than a sheet of paper. It keeps the cell’s contents in, lets nutrients through, keeps harmful substances out and carries the signals that let cells communicate. Remarkably, the core of this membrane builds itself, driven by nothing more than the chemistry of one kind of molecule and the way it interacts with water. That molecule is the phospholipid.

The phospholipid molecule

A typical phospholipid has four parts:

1. A glycerol backbone.
2. Two fatty acid chains, joined to glycerol by ester bonds (see fatty acids).
3. A phosphate group, joined to the third carbon of glycerol.
4. A small polar group attached to the phosphate, such as choline (in phosphatidylcholine), ethanolamine or serine.

The phosphate and its attached group carry electric charges, so this end is very polar: the hydrophilic head. The two fatty acid chains are non-polar: the hydrophobic tails. A molecule with both a water-loving and a water-avoiding region is called amphipathic.

Most phospholipids have one saturated tail and one unsaturated tail. The cis double bond in the unsaturated tail puts a kink in it, which becomes important for membrane fluidity.

Self-assembly: why bilayers form

Put phospholipids in water and they arrange themselves without any help. The hydrophobic tails can’t form hydrogen bonds with water, so the system reaches its lowest free energy when the tails are hidden from water and the heads face it. This is the hydrophobic effect at work (see lipids explained).

Because a phospholipid has two bulky tails, its overall shape is roughly cylindrical, and the best arrangement is a bilayer:

• two layers (leaflets) of phospholipids;
• tails pointing inwards, forming a non-polar core about 3 to 4 nm thick;
• heads facing outwards, towards the watery cytoplasm on one side and the watery surroundings on the other.

A bilayer with exposed edges would leave tails in contact with water, so bilayers naturally close up into hollow spheres, called vesicles or liposomes. This spontaneous closing is thought to have been important in the origin of the first cells. Liposomes are also used today to deliver drugs and in some vaccines.

Compare this with soap or detergent molecules, which have just one tail. Their cone-like shape makes them form micelles: small spheres with tails inside and heads outside, with no water in the middle. That’s why soaps surround grease and carry it away.

The fluid mosaic model

In 1972, S. J. Singer and Garth Nicolson proposed the fluid mosaic model, which is still the basis of how we picture membranes:

• Fluid: phospholipids aren’t fixed in place. They move sideways within their leaflet, exchanging places with neighbours millions of times per second. They rarely flip from one leaflet to the other, though, because that would drag the polar head through the non-polar core.
• Mosaic: the bilayer is studded with many different proteins, like tiles in a mosaic.

Membrane proteins

Proteins make up roughly half the mass of a typical membrane. They include:

• Channel proteins, which form water-filled pores for specific ions.
• Carrier proteins, which bind a molecule, change shape and release it on the other side.
• Pumps, which use energy (from ATP) to move ions against their concentration gradient, such as the sodium–potassium pump.
• Receptors, which bind hormones or other signals and pass a message inside the cell.
• Enzymes, bound to the membrane.
• Recognition proteins, often with carbohydrate chains attached (glycoproteins), which act as identity tags.

Proteins that span the whole membrane have a band of hydrophobic amino acids in the middle that sits comfortably among the fatty acid tails, with polar regions sticking out on each side.

Cholesterol: the fluidity buffer

Animal cell membranes contain a lot of cholesterol, a steroid lipid that slips between phospholipids with its small –OH group near the heads and its rigid rings among the tails (see cholesterol chemistry).

Cholesterol acts as a fluidity buffer:

• at high temperatures, its rigid rings restrict the movement of phospholipid tails, preventing the membrane from becoming too fluid;
• at low temperatures, it gets in the way of tails packing tightly, preventing the membrane from freezing solid.

Plants use similar molecules called phytosterols, and bacteria use other strategies.

Fluidity and temperature

A membrane must stay fluid enough for proteins to move and work, but not so fluid that it leaks. Fluidity depends on:

• Temperature: warmer means more fluid.
• Fatty acid saturation: unsaturated tails, kinked by cis double bonds, pack loosely and increase fluidity.
• Tail length: shorter tails increase fluidity.
• Cholesterol content: moderates fluidity at both extremes.

Organisms adjust their membranes to their environment. Fish living in cold water, and plants that survive frost, have membranes richer in unsaturated fatty acids, keeping them fluid in the cold. Bacteria grown at different temperatures change their fatty acid mix in the same way.

What can cross a membrane?

The non-polar core of the bilayer is a barrier to anything charged or strongly polar.

Substance	Can it cross the bilayer directly?	Why
O₂, CO₂, N₂	Yes, easily	Small and non-polar
Steroid hormones, many drugs	Yes	Non-polar, lipid-soluble
Water	Slowly	Small but polar; channels (aquaporins) speed it up
Ethanol	Yes	Small, partly non-polar
Glucose	Very slowly	Large and polar; needs carrier proteins
Ions (Na⁺, K⁺, Cl⁻)	Almost not at all	Charged; need channels or pumps

Movement happens in several ways:

• Simple diffusion: directly through the bilayer, from high to low concentration.
• Facilitated diffusion: through channel or carrier proteins, still down a concentration gradient.
• Osmosis: diffusion of water across the membrane.
• Active transport: pumps move substances against their gradient, using ATP.
• Endocytosis and exocytosis: large particles are wrapped in membrane vesicles, taking advantage of the bilayer’s ability to fuse and pinch off.

How detergents, alcohol and heat damage membranes

• Detergents have one hydrophobic tail and a polar head. They insert into bilayers and pull phospholipids and proteins into micelles, breaking the membrane apart. This is how soap and hand sanitiser destroy enveloped viruses, and how biologists extract DNA and proteins from cells.
• Organic solvents such as ethanol dissolve into the non-polar core and disrupt it.
• High temperatures make membranes excessively fluid and leaky, and denature membrane proteins. The classic beetroot practical, where pigment leaks out faster from beetroot heated to higher temperatures, shows this directly.

Key takeaways

• Phospholipids are amphipathic: a hydrophilic phosphate head and two hydrophobic fatty acid tails.
• In water they self-assemble into bilayers, driven by the hydrophobic effect; single-tailed soaps form micelles instead.
• The fluid mosaic model describes a fluid bilayer containing many proteins that transport, signal and recognise.
• Cholesterol buffers fluidity; unsaturated tails increase it.
• Small non-polar molecules cross freely; ions and large polar molecules need proteins. See the bigger picture in the four major biomolecules.