Cell Biology
Cell Membrane
Phospholipid bilayer — the selective barrier with embedded transport machinery
The cell membrane is a fluid mosaic ~5 nm thick composed of phospholipids arranged in a bilayer with hydrophilic heads facing water and hydrophobic tails inward. Cholesterol modulates fluidity. Embedded proteins (~50% of membrane mass) handle transport, signaling, and adhesion. Selective permeability lets gases and small lipophiles cross freely, but ions and large polar molecules require dedicated channels or transporters. Loss of membrane integrity is synonymous with cell death.
- Thickness~5 nm
- Composition~50% lipid, ~50% protein by mass
- Main lipidsPhosphatidylcholine, PE, PS, sphingomyelin, cholesterol
- Resting potential−70 mV (neuron); −90 mV (cardiac)
- Na/K pump stoichiometry3 Na out, 2 K in, 1 ATP
- ModelSinger-Nicolson fluid mosaic (1972)
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Why the cell membrane matters
- Pharmacology. Drug absorption, distribution, and target binding all involve membranes.
- Anesthesia. Local anesthetics block voltage-gated Na channels in nerve membranes.
- Cardiac drugs. Digoxin, antiarrhythmics, calcium channel blockers act on membrane proteins.
- Diabetes. Insulin promotes GLUT4 trafficking to muscle/fat membranes.
- Antibiotics. Polymyxins disrupt gram-negative outer membrane; amphotericin binds ergosterol.
- Cystic fibrosis. CFTR is a chloride channel — defect thickens secretions.
- Cancer. Multidrug resistance via P-glycoprotein efflux pumps in the membrane.
Common misconceptions
- Membranes are static. Fluid mosaic — lipids diffuse laterally microns per second.
- All transport requires energy. Diffusion and facilitated diffusion don't.
- Water can't cross. Water moves through aquaporins and slowly through bilayer itself.
- Cholesterol always raises fluidity. Direction depends on temperature relative to transition.
- Ion channels are open or closed. They have inactivated states (Na channels) and graded gating (Ca-activated K).
- Membrane potential equals K equilibrium. Close, but small Na and Cl permeabilities shift it.
Frequently asked questions
What types of transport cross the membrane?
Simple diffusion (O2, CO2, small lipophiles — down gradient, no protein). Facilitated diffusion (glucose via GLUT transporters — down gradient, via protein). Primary active transport (Na/K ATPase — against gradient, ATP-driven). Secondary active transport (SGLT couples Na inflow to glucose uptake — uses Na gradient). Vesicular (endocytosis, exocytosis — for macromolecules).
How does the Na/K ATPase work?
Pumps 3 Na+ out and 2 K+ in per ATP hydrolyzed. Maintains intracellular [Na] ~10 mM and [K] ~140 mM. Generates the electrochemical gradient that powers neurotransmission, nutrient uptake (SGLT, NCX), and pH balance. Consumes ~25% of resting metabolic energy. Inhibited by digoxin (cardiac glycoside) — raises intracellular Ca via NCX, increasing inotropy.
What sets resting membrane potential?
K+ leak channels and the Nernst equilibrium for K+. With high intracellular [K] and a permeable membrane, K+ leaks out, leaving negative charge inside until electrical force balances chemical. E_K ≈ −90 mV. Resting potential is more positive (~−70 in neurons) due to small Na permeability. Disturbed K levels cause arrhythmias.
What does cholesterol do?
At body temperature, cholesterol decreases fluidity (fills space between phospholipid tails) and increases stability. At low temperatures it would otherwise increase fluidity by preventing tight packing. It's essential for lipid raft formation — domains of sphingomyelin and cholesterol that organize signaling. Too much cholesterol stiffens membranes; too little destabilizes.
What are integral versus peripheral proteins?
Integral span the bilayer (transmembrane) — usually one or more α-helices through hydrophobic core. Examples: GLUT4, GPCRs, ion channels. Peripheral attach to one face via electrostatic or covalent links — often signaling adapters. Lipid-anchored proteins use GPI (outer leaflet) or prenylation/myristoylation (inner). Membrane proteins make up ~30% of the proteome.
How do drugs cross membranes?
Lipophilic drugs cross by simple diffusion (most CNS drugs). Hydrophilic drugs need transporters (e.g., levodopa via LAT1) or are confined to extracellular space (mannitol). The blood-brain barrier excludes most drugs via tight junctions and efflux pumps (P-glycoprotein). Drug design balances lipophilicity (logP 1-3) for membrane permeability without aggregation.
What happens when membranes fail?
Necrosis: ATP depletion → Na/K pump fails → cell swells → membrane ruptures → release of DAMPs → inflammation. Apoptosis: orderly disassembly with phosphatidylserine flipped to outer leaflet (signal for phagocyte uptake). Hemolysis: RBC membranes lyse from osmotic stress, complement attack, or genetic disorders (hereditary spherocytosis). Membrane attack complex (MAC) of complement creates lethal pores.