Difficulty: Introductory to Intermediate | Prerequisites: Familiarity with cell compartments (see Part 1 notes)
Cell membranes are built from a phospholipid bilayer studded with proteins, described by the fluid mosaic model. Small nonpolar molecules pass through freely, but ions and large polar molecules need dedicated transport proteins or vesicle-based mechanisms. Understanding how the membrane controls what gets in and out is essential for almost every topic that follows in cell biology.
Lipid bilayer
The double layer of phospholipids forming the structural core of all cell membranes. Hydrophilic (water-loving) heads face outward; hydrophobic (water-fearing) tails face inward. Think of it as two rows of molecules standing back to back, creating a greasy interior that most water-soluble substances cannot cross.
Fluid mosaic model
The accepted model describing the cell membrane as a fluid combination of lipids and proteins that can move laterally within the plane of the membrane. In simple terms, the membrane is a flexible, shifting sea of lipids with proteins floating in it, not a rigid wall.
Integral (transmembrane) protein
A protein embedded in the lipid bilayer, spanning part or all of its thickness. Serves functions including transport, signalling, and structural anchoring. Think of it as a protein threaded through the membrane like a bolt through a wall.
Peripheral protein
A protein attached to the surface of the membrane (inner or outer face) rather than embedded within it. In simple terms, these sit on the membrane rather than passing through it.
Passive diffusion
The movement of molecules across a membrane down their concentration gradient, requiring no energy input. Think of it as molecules drifting from where there are more of them to where there are fewer, on their own.
Facilitated diffusion
Diffusion assisted by specific carrier or channel proteins, still moving down the concentration gradient with no energy cost. In simple terms, the molecule still flows downhill, but it needs a protein to open the door for it.
Active transport
The movement of substances across a membrane against their concentration gradient, requiring energy (typically ATP). Think of it as pumping molecules uphill, which costs energy.
Endocytosis
The process by which a cell takes in material by engulfing it in a portion of the plasma membrane, forming a vesicle. In simple terms, the cell wraps its membrane around something outside and pulls it in.
Exocytosis
The process by which a cell expels material by fusing a vesicle with the plasma membrane, releasing its contents outside the cell. Think of it as the reverse of endocytosis: a package inside the cell merges with the membrane and dumps its cargo out.
The structural backbone of every cell membrane
Each phospholipid has a hydrophilic (polar) head and two hydrophobic (nonpolar) fatty acid tails
The tails face inward, creating a hydrophobic interior that blocks free passage of most polar and charged molecules
This arrangement is self-assembling in aqueous environments
Proposed by Singer and Nicolson (1972)
Describes the membrane as a two-dimensional fluid in which lipids and proteins move laterally
Proteins are distributed in a mosaic pattern throughout the lipid bilayer
Membrane fluidity is influenced by cholesterol content and the saturation of fatty acid tails (more unsaturated tails = more fluid)
Integral (transmembrane) proteins: span the bilayer partly or fully; involved in transport (channels, carriers), signalling (receptors), and enzymatic activity
Peripheral proteins: loosely attached to the inner or outer membrane surface; often involved in signalling cascades or maintaining cell shape
Together, membrane proteins account for transport, cell-cell recognition, enzymatic activity, signal transduction, intercellular joining, and attachment to the cytoskeleton
Small, nonpolar molecules (O2, CO2, N2) cross the bilayer freely by passive diffusion
Small, uncharged polar molecules (water, ethanol) cross slowly
Large polar molecules (glucose, amino acids) and ions (Na+, K+, Ca2+, Cl-) cannot cross unaided and require protein channels or carriers
No energy required
Molecules move down their concentration gradient (high to low)
Only small nonpolar molecules cross this way at a meaningful rate
Rate depends on the steepness of the gradient and the molecule's size and polarity
Still passive (no energy), still moves down the gradient
Requires specific membrane proteins:
Channel proteins: form pores that allow specific ions or small molecules through (e.g. aquaporins for water)
Carrier proteins: bind a specific molecule, change shape, and release it on the other side
Saturable: once all available channels or carriers are occupied, the rate plateaus
Requires energy, typically from ATP hydrolysis
Moves substances against their concentration gradient (low to high)
Example: the Na+/K+ ATPase, which pumps 3 Na+ out and 2 K+ in per ATP molecule
Essential for maintaining ion gradients that drive nerve impulses, muscle contraction, and secondary active transport
Endocytosis: the membrane invaginates and pinches off to form an intracellular vesicle containing extracellular material
Subtypes include phagocytosis ("cell eating"), pinocytosis ("cell drinking"), and receptor-mediated endocytosis
Exocytosis: intracellular vesicles fuse with the plasma membrane and release their contents outside the cell
Used for secretion of hormones, neurotransmitters, and enzymes
Both processes also serve to add or remove membrane proteins and lipids from the cell surface
Selective permeability is why drug delivery is hard: most pharmaceutical molecules are too large or too polar to cross membranes unaided, which is why drug design focuses on making molecules lipophilic enough to enter cells or targeting specific transport proteins. The Na+/K+ ATPase is the basis for how nerve cells fire and how your heart maintains its rhythm.
Students often think "selectively permeable" means the membrane chooses what to let through in an active, decision-making sense. It does not; selectivity is a physical property of the bilayer and its embedded proteins.
Facilitated diffusion is frequently confused with active transport. The key difference: facilitated diffusion requires no energy and moves molecules down their gradient. Active transport uses energy and moves molecules against their gradient.
Water does cross the bilayer slowly on its own, but most water movement in cells goes through aquaporin channels. Students sometimes think water cannot cross at all without a channel.
Students sometimes forget that endocytosis and exocytosis are also transport mechanisms. They tend to focus only on diffusion and active transport.
Be able to rank molecules by membrane permeability: small nonpolar > small uncharged polar > large polar > ions. This ranking appears in multiple-choice questions regularly.
Know the difference between passive diffusion, facilitated diffusion, and active transport. Exams commonly give you a scenario and ask which type of transport is at work.
The Na+/K+ ATPase (3 Na+ out, 2 K+ in, 1 ATP) is a favourite exam question. Know the stoichiometry.
Understand why the hydrophobic interior of the bilayer is the barrier. This is the conceptual foundation for all permeability questions.
True or false: Active transport moves molecules down their concentration gradient.
False. Active transport moves molecules against their gradient and requires energy.
Fill in the blank: The model that describes the membrane as a fluid combination of lipids and proteins is called the ______ model.
Fluid mosaic model.
True or false: Ions such as Na+ and K+ can freely diffuse across the lipid bilayer.
False. Ions are charged and cannot cross the hydrophobic interior without protein channels or carriers.
True or false: Facilitated diffusion requires ATP.
False. Facilitated diffusion is passive; it uses protein channels or carriers but no energy.
Fill in the blank: The process by which a cell engulfs extracellular material by wrapping membrane around it is called ______.
Endocytosis.
Q: A cell is placed in a solution where the concentration of glucose is higher outside than inside. Glucose enters the cell via a carrier protein. What type of transport is this?
A: Facilitated diffusion. Glucose is moving down its concentration gradient (high outside to low inside) through a carrier protein, so no energy is required.
Q: Explain why oxygen (O2) can cross the membrane freely but sodium ions (Na+) cannot.
A: Oxygen is a small, nonpolar molecule that dissolves easily in the hydrophobic lipid bilayer interior. Sodium ions carry a positive charge, which makes them repelled by the hydrophobic core. Na+ requires a channel or carrier protein to cross.
Q: What is the role of the Na+/K+ ATPase, and why is it classified as active transport?
A: The Na+/K+ ATPase pumps 3 Na+ ions out of the cell and 2 K+ ions in per ATP hydrolysed. It is active transport because it moves both ions against their respective concentration gradients, requiring energy from ATP.
Q: How does cholesterol affect membrane fluidity?
A: At physiological temperatures, cholesterol reduces fluidity by restricting phospholipid movement. At low temperatures, it prevents the membrane from becoming too rigid by disrupting tight packing of phospholipid tails. It acts as a fluidity buffer.
Q: Distinguish between phagocytosis and pinocytosis.
A: Phagocytosis ("cell eating") involves engulfing large particles such as bacteria or debris. Pinocytosis ("cell drinking") involves taking in small droplets of extracellular fluid along with dissolved solutes. Both are forms of endocytosis.
Membrane transport is the foundation for understanding signal transduction (how receptors on the membrane trigger intracellular cascades), neurophysiology (action potentials depend entirely on ion gradients maintained by active transport), and the endomembrane system (vesicular traffic between ER, Golgi, and the plasma membrane is endocytosis and exocytosis at work). The clinical correlations in Part 3 of these notes, such as lysosomal storage diseases, connect directly to defects in membrane-bound compartments and their transport pathways.
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