Plasma Membrane: Study Guide (Biology 2.3)

A thin boundary that keeps the inside different

Every cell is surrounded by watery fluid, and every cell is full of watery fluid (the cytosol). Yet the two fluids are different. The cytosol holds different amounts of ions, sugars and proteins from the fluid outside. The plasma membrane is what keeps them different. It is only a few nanometres thick, but it controls what goes in and out, it carries the cell’s detectors, and it lets the cell recognise its neighbours.

To understand how such a thin layer does all this, you need two ideas you met in Unit 1: which molecules are hydrophilic (“water-loving”, polar or charged) and which are hydrophobic (“water-fearing”, nonpolar). The whole structure of the membrane follows from where each part is most stable.

Phospholipids: heads out, tails in

A phospholipid has a polar head containing a phosphate group and two nonpolar fatty acid tails (Topic 1.5). One end is hydrophilic and the other is hydrophobic.

Put many phospholipids in water and they arrange themselves into a bilayer:

• The polar heads face outwards, into the watery fluid. In a plasma membrane, one layer of heads faces the extracellular fluid and the other faces the cytosol.
• The nonpolar tails of the two layers point towards each other and form the hydrophobic interior of the membrane.

Why this way round? The heads can form hydrogen bonds and other attractions with water, so they are stable at the surface. The tails cannot. If tails were exposed, water molecules would have to arrange themselves around them without hydrogen-bonding to them, which is unstable. Tucking the tails together, away from water, is the most stable arrangement. No energy from the cell is needed: the bilayer forms and reseals itself on its own.

The hydrophobic interior is the key to the membrane’s job as a barrier. Ions and polar molecules are attracted to water and do not easily enter the oily middle. You will see exactly what can and cannot cross in Topic 2.4.

Membrane proteins: R groups decide where each part sits

Proteins are set into the bilayer. A protein’s surface is made of the R groups (side chains) of its amino acids (Topic 1.7). Some R groups are nonpolar; others are polar or charged. The same rule as for phospholipids decides where each part of the protein ends up:

• Hydrophobic regions (nonpolar R groups) form the part of the protein’s surface that touches the fatty acid tails in the middle of the membrane.
• Hydrophilic regions (polar and charged R groups) are either exposed to the cytosol (or to the outside fluid), or they are inside the protein, for example lining a water-filled pore that runs through it.

So a protein can be hydrophilic, hydrophobic, or both. Two types are worth naming:

• Integral (transmembrane) proteins pass right through the bilayer. They have a hydrophobic middle section and hydrophilic ends on each side. Many contain an α-helix of about 20 or more mostly nonpolar amino acids that spans the hydrophobic interior.
• Peripheral proteins sit on one surface only. They attach to the heads or to an integral protein, and they do not enter the hydrophobic interior. Their surface is mostly hydrophilic.

Membrane proteins do many jobs: channels and carriers move ions and polar molecules across; receptors detect signals; some are enzymes; others anchor the membrane to the cytoskeleton inside or to neighbouring cells.

The fluid mosaic model

The modern picture of the membrane is called the fluid mosaic model.

• Mosaic: the membrane is a patchwork of different molecules. Phospholipids form the framework. Set into it are proteins, steroids such as cholesterol (in vertebrate animal cells), glycoproteins (proteins with carbohydrate chains attached) and glycolipids (lipids with carbohydrate chains attached).
• Fluid: these components are not fixed in place. They can move sideways (laterally) within the membrane, like people moving around in a crowd. The membrane holds together because of hydrophobic and hydrophilic interactions, not covalent bonds between neighbours.

What each component does for the cell

Component	Structure	Role in keeping the internal environment steady
Phospholipids	polar head, two nonpolar tails; bilayer	form the framework and the hydrophobic barrier that stops ions and polar molecules leaking across
Integral proteins	hydrophobic middle in the tails, hydrophilic ends or pores	channels and carriers let specific hydrophilic substances cross; receptors pass on signals
Peripheral proteins	hydrophilic, on one face only	enzymes, signalling, attachment to the cytoskeleton
Cholesterol (vertebrate animals)	steroid; four fused rings, sits among the tails	helps keep the membrane stable and its fluidity within a working range as temperature changes
Glycoproteins	protein with a carbohydrate chain on the outer face	cell recognition (for example, the immune system telling “self” from “non-self”), cell-to-cell adhesion, receiving signals
Glycolipids	lipid with a carbohydrate chain on the outer face	cell recognition and adhesion

Background: the two layers are not identical. Carbohydrate chains are found only on the outer face, and some proteins face only one side. Phospholipids rarely flip from one layer to the other. Some proteins are held in place by the cytoskeleton, so not every component moves freely.

Reading membrane diagrams

Questions often give you a membrane diagram and ask you to describe it. Use these clues:

1. Which side is outside? Carbohydrate chains point to the outside of the cell.
2. Which layer is which? Heads (circles or blobs) face the water on each side. Tails (lines) meet in the middle.
3. Integral or peripheral? If a protein passes through the tail region, it is integral. If it only touches one surface, it is peripheral.
4. Hydrophobic or hydrophilic region? Any part of a protein that touches the tails is hydrophobic. Any part facing the fluid on either side, or lining a pore, is hydrophilic.

A diagram is a model, so know its limits. Figure 1 is not to scale (proteins vary greatly in size). It is a still picture of a membrane that is really moving all the time. It shows only a few proteins, whereas real membranes are crowded with them. It is also a flat slice of a curved, three-dimensional surface.

Worked example 1: will this protein span the membrane?

Question. Two fictional protein segments are shown below, each as a string of letters read from one end to the other. N = amino acid with a nonpolar R group; P = polar, uncharged R group; C = charged R group. Assume each segment folds as an α-helix, which rises 0.15 nm for every amino acid. The hydrophobic interior of the membrane is roughly 3 to 4 nm thick.

Segment A: CPPCN NNNNN NNNNN NNNNN NNNNN PCCPC

Segment B: PCPNP CNNNN NNNNN CPPCP NNPCP PCPC

(a) For each segment, find the longest run of nonpolar amino acids and its length as a helix. (b) Which segment is likely to be a transmembrane region? Describe how it sits in the membrane. (c) Predict the effect of changing the 15th amino acid of segment A from N to C.

(a) Longest nonpolar runs.

1. Segment A: positions 5 to 25 are all N. That is 21 nonpolar amino acids in a row.
2. Length as a helix: 21 × 0.15 nm = 3.15 nm.
3. Segment B: the longest run is positions 7 to 15, only 9 amino acids. Length: 9 × 0.15 nm = 1.35 nm.

Check. How many residues are needed to cross 3 to 4 nm? 3 ÷ 0.15 = 20 and 4 ÷ 0.15 ≈ 27. So about 20 to 27 nonpolar amino acids are needed.

(b) Interpretation. Segment A’s nonpolar run (3.15 nm) is long enough to cross the hydrophobic interior. Its nonpolar R groups face the fatty acid tails. The polar and charged amino acids at each end sit at the surfaces, among the heads and in the watery fluid on each side. Segment B’s run (1.35 nm) is far too short to span the interior, and it is broken up by charged amino acids. It is more likely to be part of a region that stays in the cytosol or the outside fluid.

(c) Prediction. A charged R group would sit in the middle of the hydrophobic interior, surrounded by nonpolar tails it cannot interact with. That is unstable. The helix would be less likely to stay in the membrane, so the protein might not insert properly or might fold differently, and its function (for example as a channel) could be lost.

Worked example 2: evidence that the membrane is fluid

Question. In a fictional experiment, two different membrane proteins, X and Y, were each tagged with a fluorescent label in separate cultures of the same cell type. A laser bleached the label in a small spot on the cell surface, so that spot went dark. The brightness of the spot was then measured. A third culture with protein X tagged was first fixed with a chemical that cross-links proteins so they cannot move.

Before bleaching, every spot read 1000 units; just after bleaching, every spot read 200 units.

Time after bleaching / s	0	10	30	60	120
Protein X / units	200	560	800	900	920
Protein Y / units	200	240	300	340	360
Fixed cells (X) / units	200	205	200	210	205

(a) Calculate the percentage of fluorescence recovered at 120 s for each sample. (b) Explain what the recovery of protein X shows about the membrane. (c) Suggest why protein Y recovered much less, and explain the purpose of the fixed cells.

(a) Calculation. The bleach removed 1000 − 200 = 800 units. Percentage recovered = (reading − 200) ÷ 800 × 100.

1. Protein X: (920 − 200) ÷ 800 × 100 = 720 ÷ 800 × 100 = 90%.
2. Protein Y: (360 − 200) ÷ 800 × 100 = 160 ÷ 800 × 100 = 20%.
3. Fixed cells: (205 − 200) ÷ 800 × 100 ≈ 0.6%, effectively zero.

(b) Protein X. The bleached molecules did not repair themselves. Instead, unbleached tagged proteins from the surrounding membrane moved sideways into the dark spot, and bleached ones drifted out. Most of the brightness returned within a minute. This supports the “fluid” part of the model: membrane proteins can move laterally within the bilayer.

(c) Protein Y and the fixed cells. Protein Y moved much less: only 20% recovered in 2 minutes, so most of it did not move into the spot in that time. A reasonable explanation is that much of protein Y is anchored, for example attached to the cytoskeleton or to a large protein complex. This is consistent with the model, which allows some components to be held in place. The fixed cells are a control: when movement is blocked, there is no recovery. This shows that the recovery seen for X was caused by movement, not by the label recovering on its own.

How confident? Each value is from one fictional run, so repeats would be needed before drawing firm conclusions, and anchoring is only one possible explanation for Y. Testing Y in cells whose cytoskeleton has been disrupted would be a sensible next step.

Common misconceptions

• “The tails face the water and the heads face inwards.” Reversed. Heads are hydrophilic and face the watery fluid on both sides; tails are hydrophobic and face each other.
• “A plasma membrane is one layer of phospholipids.” It is two layers (a bilayer). Each layer has its heads facing a different fluid.
• “All of a membrane protein is hydrophobic.” Only the part touching the tails is. The ends that face the fluids and the lining of any pore are hydrophilic.
• “Proteins float on top of the membrane.” Peripheral proteins sit on a surface, but integral proteins pass right through the bilayer.
• “Fluid means the membrane is liquid and has no structure.” The membrane holds a stable bilayer shape. “Fluid” means its components can drift sideways within it.
• “Carbohydrate chains are on both faces.” In the plasma membrane they face the outside of the cell.
• “Cholesterol is found in every membrane.” Cholesterol is the membrane steroid of animal cells (the course names vertebrate animals). Plants and fungi use related sterols instead, and most bacteria have no sterols in their membranes at all.
• “The cell has to spend energy to hold the bilayer together.” The bilayer forms and stays together on its own because of how heads and tails interact with water.

Where this leads

The hydrophobic interior you have just met explains which substances can cross a membrane by themselves and which need a protein to help. That is the next topic, membrane permeability. If you want to look back at why cells stay small, see the Topic 2.2 study guide. Test yourself with the practice questions, then use the revision notes and the checklist to consolidate.