Chapter 3: The Cell Membrane

The cell membrane is far more than a bag holding the cytoplasm in. It's a selectively permeable, dynamically active structure — and it's built from the same three macromolecule classes covered in earlier chapters: protein, lipid, and carbohydrate.

Composition: roughly protein, lipid, carbohydrate

By mass, a typical plasma membrane is about:

• Protein — 49%
• Lipid — 43% (phospholipids, glycolipids, and cholesterol)
• Carbohydrate — 8% (as chains attached to outer-leaflet lipids and proteins, forming glycolipids and glycoproteins)

The lipid bilayer, in cross-section

Membrane lipids

The lipid component itself has three parts: phospholipids (the bilayer's structural backbone), glycolipids (carbohydrate-bearing lipids on the outer leaflet, involved in cell recognition), and cholesterol (interspersed through the bilayer, stabilizing fluidity across a range of temperatures).

Integral vs. peripheral membrane proteins

• Integral proteins are embedded in — often spanning — the lipid bilayer. Most receptors, ion channels, and transporters are integral, transmembrane proteins.
• Peripheral proteins attach loosely to the membrane surface (often to an integral protein or a lipid head group) without inserting into the bilayer itself.

Three functions of the cell membrane

1. Maintains and preserves cell shape.
2. Protects the cell, allowing it to withstand mechanical stress — for example squeezing through small capillaries — by deforming without changing its own composition.
3. Transports substances into and out of the cell:
   • Passive transport — diffusion, osmosis; moves down a concentration gradient, no energy required.
   • Active transport — ion pumps; moves against a gradient, requires ATP.

Clinical vignette: ACE2, the spike protein, and SARS-CoV-2

Membrane receptor proteins are ordinarily beneficial — but their molecular specificity can be turned against the host. ACE2 (angiotensin- converting enzyme 2) is a membrane-bound enzyme normally expressed on cells of the airway, lung, gut, heart, and kidney.

SARS-CoV-2's spike (S) protein acts as a ligand that binds ACE2 with high affinity — using it as its entry receptor rather than for ACE2's normal enzymatic role. A host protease, TMPRSS2, then cleaves the spike protein, activating it for membrane fusion. Once the viral membrane fuses with the host membrane, only the viral RNA genome enters the cell — the protein "coat" is left behind at the cell surface.

This single receptor–ligand interaction explains several clinically important facts at once:

• Why COVID-19 affects the organs it does (wherever ACE2 is expressed).
• Why drugs that block the TMPRSS2 cleavage step (e.g. nafamostat, camostat mesylate) or the spike–ACE2 interaction can blunt infection.
• Why antiviral strategy more broadly targets specific steps of this cycle — entry, RNA replication (remdesivir, favipiravir), or release (oseltamivir, amantadine) — each corresponding to a distinct biochemical step in the viral life cycle.

Key teaching point

The membrane's protein content isn't incidental — "remember, one component of the cell membrane is protein" is the single fact that explains both normal signaling (hormone receptors) and one of the most consequential infections in modern medicine (ACE2 as the doorway for SARS-CoV-2). Membrane biochemistry and receptor pharmacology are the same subject viewed from two angles.