Membrane structure & permeability

Phospholipids build a bilayer by themselves

The main building block of a membrane is the phospholipid. It has a glycerol backbone attached to two fatty-acid tails and a phosphate-containing head. The head is charged or polar, so it's hydrophilic and mixes with water. The tails are long chains of carbon and hydrogen, so they're hydrophobic and don't.

A molecule with one water-loving end and one water-avoiding end is called amphipathic. Put phospholipids in water and they arrange themselves, without any help, into a phospholipid bilayer: two layers with the heads facing the water on each side and the tails tucked together in the middle.

Nothing is pulling them into place. The bilayer forms because of the hydrophobic effect: water molecules are freer when the oily tails are hidden away together, so that arrangement is the most stable one. The same effect makes a punctured membrane seal itself back up.

The fluid mosaic model

Before 1972, a popular model pictured the membrane as a sandwich, with lipids as the filling and flat sheets of protein as the bread. Electron microscopy and experiments like Frye and Edidin's didn't fit it. In 1972, S. J. Singer and Garth Nicolson proposed the fluid mosaic model: a fluid bilayer with proteins floating in it, like tiles in a mosaic that can move around.

• Integral proteins are embedded in the bilayer. Many span it completely: their stretches of hydrophobic amino acids sit in the oily core, and their hydrophilic parts stick out on either side. Channels, carriers and pumps are integral proteins.
• Peripheral proteins sit on the inner or outer surface, attached to lipid heads or to integral proteins. They act as enzymes, anchor the cytoskeleton, or help cells recognise each other.
• Cholesterol is tucked between the phospholipids in animal cell membranes and helps control how fluid the membrane is.
• Glycoproteins and glycolipids are proteins and lipids with sugar chains attached. The sugars face only the outside of the cell and form a sugary coat, the glycocalyx, used in cell recognition. It's part of how your immune system tells your own cells from invaders.

The whole membrane is only 5–10 nm thick. By mass, a typical human cell membrane is roughly half protein, 40% lipid and 10% carbohydrate, though this varies a lot between cell types.

How fluid is it, and what controls that?

A membrane isn't a rigid wall with fixed holes. Within each leaflet, lipids swap places with their neighbours millions of times a second, and many proteins drift sideways too, as Frye and Edidin saw. Cells need this fluidity: membrane proteins have to move and change shape, and vesicles have to bud off and fuse. But too fluid, and the membrane leaks and falls apart. Three things set the balance:

• Temperature. Warmth makes the lipids move more and the membrane more fluid. Cold slows them down, and eventually the membrane can stiffen into a gel.
• Fatty-acid saturation. A saturated fatty acid has no C=C double bonds, so its tail is straight and packs tightly against its neighbours. An unsaturated tail has one or more double bonds that put kinks in it, so the lipids can't pack as closely and the membrane stays fluid at lower temperatures.
• Cholesterol. It acts as a fluidity buffer. At warm temperatures its rigid rings hold neighbouring phospholipids still, making the membrane less fluid. At cool temperatures it wedges the phospholipids apart so they can't pack tightly, keeping the membrane from freezing up. The result is a membrane that works over a wider range of temperatures.

Many organisms actively adjust their membranes. Put bacteria, plants or cold-blooded animals in the cold and they increase the proportion of unsaturated fatty acids in their membranes, keeping fluidity roughly constant. This is called homeoviscous adaptation.

What can get through?

The oily core of the bilayer decides what can cross without help. A molecule has to leave water, dissolve in the hydrophobic middle, and come out the other side. That's easy for some molecules and nearly impossible for others. So the membrane is selectively permeable. Roughly, from fastest to slowest:

1. 1Small nonpolar molecules, such as O₂, CO₂ and N₂, and lipid-soluble molecules such as steroid hormones, dissolve in the core and slip straight through.
2. 2Small uncharged polar molecules, such as water, urea, glycerol and ethanol, cross, but more slowly.
3. 3Large polar molecules, such as glucose, cross extremely slowly.
4. 4Ions, such as Na⁺, K⁺, Cl⁻ and H⁺, practically can't cross at all. Their charge holds a shell of water molecules around them, and stripping it off to enter the oily core takes far too much energy.

Anything that the bilayer blocks, but the cell needs to move, has to go through a transport protein. That's the subject of the next topic.

Key terms

Amphipathic

Having both a hydrophilic part and a hydrophobic part, like a phospholipid.

Phospholipid bilayer

Two layers of phospholipids with heads facing out and tails facing each other in the middle.

Fluid mosaic model

The model of the membrane as a fluid lipid bilayer with proteins that can move within it.

Integral / peripheral protein

A protein embedded in the bilayer / a protein attached to its surface.

Glycocalyx

The coat of sugar chains on glycoproteins and glycolipids outside the cell, used in recognition.

Saturated / unsaturated fatty acid

A straight tail with no C=C double bonds / a kinked tail with one or more C=C double bonds.

Selectively permeable

Letting some substances cross easily while blocking others.

Homeoviscous adaptation

Adjusting membrane lipid composition to keep fluidity roughly constant as temperature changes.

Check yourself

Try answering in your head before you open each answer.

• 1.If Frye and Edidin had kept their hybrid cells at 5 °C instead of 37 °C, what would you expect to see after 40 minutes? What does this tell you about how the proteins move?Show answerHide

  The colours would still be mostly separated, because the membrane is less fluid in the cold and the proteins drift much more slowly. Combined with the fact that ATP poisons didn't stop the mixing, the simplest explanation is that the proteins drift by diffusion within a fluid membrane rather than being actively carried.

• 2.A fish lives in water near 0 °C. Would you expect its cell membranes to contain more saturated or more unsaturated fatty acids than a fish from warm tropical water? Explain.Show answerHide

  More unsaturated. The kinks in unsaturated tails stop phospholipids packing tightly, so the membrane stays fluid enough to work in the cold instead of stiffening into a gel.

• 3.Oestrogen (a steroid) acts on receptors inside its target cells, while insulin (a protein) acts on a receptor on the cell surface. Explain this difference using membrane permeability.Show answerHide

  Oestrogen is lipid-soluble, so it can cross the bilayer and reach receptors inside the cell. Insulin is large and polar, so it can't cross the hydrophobic core and has to signal through a receptor in the plasma membrane.