Movement of Substances Through Membranes
A complete guide to how particles enter and leave cells — from simple diffusion to active pumps and vesicle-mediated bulk transport.
Membrane Permeability
Before we can understand how substances move through cell membranes, we must understand what permeability means and why cell membranes are not simply open or closed — they are selectively permeable, choosing what passes based on molecular properties.
- Permeability determines which substances enter or leave cell cytoplasm
- Cell membranes are not simply open or closed — they are selective
- This selectivity is fundamental to maintaining homeostasis
- Three types of permeability exist across a spectrum
- Impermeable membranes block all substances
- Freely permeable membranes allow everything
- Cell membranes are selectively permeable (semipermeable)
- Selection is based on size, electric charge, and lipid solubility — or combinations
- Small nonpolar molecules cross freely; large or charged ones are blocked
- Cell membranes are optimally designed as selectively permeable barriers
- This selective control is the basis for all transport mechanisms in this chapter
- Without selective permeability, cells could not maintain their internal environment
Permeability of a membrane determines which substances can enter or leave the cytoplasm of cells. Cell membranes are selectively permeable (semipermeable), meaning they allow the passage of only certain substances and restrict others. Selection is based on size, electric charge, lipid solubility, or a combination of these factors.
Passive vs Active Transport
All membrane transport falls into two fundamental categories: passive transport (no energy needed, particles go downhill) and active transport (energy required, particles go uphill). Understanding this distinction is the foundation of the entire chapter.
- Two fundamental transport mechanisms exist for all membrane movement
- Direction relative to concentration gradient is the defining feature
- Energy usage distinguishes the two types completely
- Passive transport: particles move high → low concentration (downhill)
- Passive transport does NOT require ATP
- Active transport: particles move low → high concentration (uphill)
- Active transport requires ATP energy to power pumps
- The concentration difference is called the concentration gradient
- Every transport mechanism in this chapter is either passive or active
- Passive = diffusion, osmosis, facilitated diffusion
- Active = primary and secondary active transport, vesicular transport
| Feature | Passive Transport | Active Transport |
|---|---|---|
| Direction | High → Low concentration (downhill) | Low → High concentration (uphill) |
| Energy (ATP) | Not required | Required |
| Driving force | Concentration gradient | ATP hydrolysis (or stored ion gradient) |
| Examples | Diffusion, Osmosis, Facilitated diffusion | Na⁺/K⁺ pump, Ca²⁺ pump, secondary cotransport |
| Proteins needed? | Sometimes (facilitated) | Always (carrier/pump proteins) |
Simple Diffusion
Diffusion is the most fundamental form of passive transport. All atoms and molecules in motion naturally move from regions of high concentration to low concentration — no protein, no energy required. Understanding diffusion is the gateway to all other transport mechanisms.
- Diffusion is the net movement of particles from high to low concentration
- It requires only kinetic energy from heat — no cellular ATP
- It is the simplest and most universal form of membrane transport
- Occurs in all states of matter; key in biology for gases and lipid-soluble molecules
- All molecules above 0 K have kinetic energy and move constantly and randomly
- Net flux always goes from high → low concentration (the concentration gradient)
- Three factors affect diffusion rate: temperature, molecular size/mass, medium density
- Only small, nonpolar (hydrophobic) molecules cross the lipid bilayer by simple diffusion
- Polar and charged molecules cannot enter the hydrophobic core of the membrane
- Simple diffusion applies to: O₂, CO₂, fatty acids, steroid hormones, and water
- Diffusion stops when the concentration gradient disappears (equilibrium)
- Ions and polar molecules need protein assistance — this leads to facilitated diffusion
Diffusion is the net movement of particles from areas of higher concentration to areas of lower concentration. The concentration difference between two regions is called the concentration gradient — this is the sole driving force. No ATP is required. Diffusion stops when equilibrium is reached.
Oxygen dissolved in water diffuses more slowly than in air. Water is denser — there are more collisions between molecules, slowing the diffusion rate. This explains why aquatic organisms have specialized gills to maximize oxygen uptake despite the slower diffusion rate in water.
- Oxygen (O₂) — small, nonpolar
- Carbon dioxide (CO₂) — small, nonpolar
- Fatty acids — lipid-soluble
- Steroid hormones (testosterone, estrogen)
- Water (H₂O) — small & uncharged, crosses despite polarity
- Na⁺, K⁺, Cl⁻, Ca²⁺ ions — charged
- Glucose — too polar and too large
- Amino acids — polar
- ATP, proteins — far too large
- Most polar organic molecules
The interior of the lipid bilayer is hydrophobic (nonpolar). Polar molecules and ions are strongly attracted to the water molecules on either side of the membrane. They cannot enter the nonpolar core — like oil and water refusing to mix. This is what makes the membrane a selective barrier.
Osmosis
Osmosis is the diffusion of water — a specific and vital form of passive transport. Because biological membranes are semipermeable, water moves freely but most solutes cannot. This creates osmotic pressure that drives enormous biological processes from kidney function to cell volume regulation.
- Osmosis is the specific diffusion of water across a semipermeable membrane
- Water moves from where it is more concentrated to where it is less concentrated
- Higher solute concentration = lower water concentration
- Osmolarity measures the total concentration of all dissolved particles
- Osmolarity units: osmoles/L (one osmole = one mole of dissolved particles)
- 1M NaCl = 2 osmol/L (dissociates into Na⁺ + Cl⁻)
- 1M MgCl₂ = 3 osmol/L (Mg²⁺ + 2Cl⁻)
- Osmotic pressure = tendency of water to move into a solution
- Cells in isotonic solution: no net water flow; hypotonic: swell; hypertonic: shrink
- Osmosis regulates water movement throughout the entire body
- Critical for water absorption (intestines), kidney tubule reabsorption, and cell volume
- IV fluids must be isotonic to prevent cell damage
- Greater osmolarity → lower water concentration → water flows in by osmosis
Osmosis is the net movement of water from a region of high water concentration to a region of low water concentration across a semipermeable membrane. Water molecules can pass freely in both directions, but the net movement is always toward the more concentrated solution (lower water concentration). Solutes (salts, glucose) cannot diffuse freely across the membrane.
Osmolarity = total solute concentration of a solution, including all dissolved particles. One osmole = one mole of solute particles. The key rule: Higher osmolarity = more dissolved particles = lower water concentration.
| Solution | Molarity | Dissociation | Osmolarity |
|---|---|---|---|
| Glucose | 1 M | No dissociation (stays as 1 particle) | 1 osmol/L |
| NaCl | 1 M | Na⁺ + Cl⁻ = 2 ions | 2 osmol/L |
| MgCl₂ | 1 M | Mg²⁺ + 2Cl⁻ = 3 ions | 3 osmol/L |
| Solution Type | Concentration vs Cell | Net Water Flow | Cell Effect | Clinical Relevance |
|---|---|---|---|---|
| Isotonic | Equal to cell | No net flow | Normal shape maintained | Safe IV saline = 0.9% NaCl |
| Hypotonic | More dilute than cell | INTO the cell | Cell swells → may lyse (burst) | Excess plain water IV can lyse RBCs |
| Hypertonic | More concentrated than cell | OUT of the cell | Cell crenates (shrinks) | Dehydration causes cell shrinkage |
Osmosis is fundamental to life. It governs water absorption in the digestive system (gut lumen → blood), water delivery to cells from blood capillaries, water reabsorption in kidney tubules (concentrating urine), and overall cell volume regulation throughout the body.
Facilitated Diffusion
Many molecules that cells need — glucose, ions — cannot cross the lipid bilayer by themselves. Protein channels and carriers act as molecular gates and shuttles, allowing these molecules to cross passively (still no ATP) down their concentration gradient. This is facilitated diffusion.
- Charged ions and large polar molecules cannot enter the hydrophobic bilayer
- Integral membrane proteins act as channels or carriers to facilitate passage
- Still passive — movement is always down the concentration gradient
- No ATP is required — the concentration gradient provides the energy
- Channel proteins form hydrophilic pores — ions flow through
- Channels are selective, gated (ligand-gated or voltage-gated), and usually closed
- Carrier proteins bind substrate and change shape (conformational change)
- Carriers are highly specific, can become saturated, and also require no ATP
- Both types are always transmembrane proteins spanning the full bilayer
- Key example: GLUT glucose carriers allow continuous glucose uptake into cells
- Ion channels create the electrochemical gradient (concentration + electrical force)
- Carrier saturation is a fundamental limit on transport capacity
- Exception: Intestines and kidneys use active transport for glucose, not facilitated
Charged ions (Na⁺, K⁺, Cl⁻, Ca²⁺) diffuse through the plasma membrane with the help of channel proteins. The transmembrane portion forms a hydrophilic channel through which ions can enter or leave cells. Channels are selective — only certain ions pass. They are usually closed and require a specific stimulus to open.
- A specific molecule (ligand) binds to the channel protein
- Binding opens or closes the channel
- Example: Acetylcholine opens certain ion channels at neuromuscular junctions
- Controlled by chemical signals
- Changes in electrical charge distribution across the membrane open/close the channel
- Critical for action potentials in nerve and muscle cells
- The inside of most cells is more negatively charged than outside
- This electrical difference attracts positive ions and repels negative ions
Ion movement through channels is driven by both the concentration gradient AND the electrical gradient across the membrane. Together, these two driving forces are called the electrochemical gradient. The inside of most plasma membranes is more negatively charged — this attracts positive ions inward.
Molecules like glucose are too polar and too large for channels. Specific carrier proteins bind the substrate, change their shape (conformational change) — moving the binding site to the opposite side of the membrane — and release the substrate. No ATP is needed. The process can become saturated when all binding sites are occupied.
GLUT carrier proteins transport glucose into most body cells by facilitated diffusion. Glucose is metabolized almost immediately upon entry, keeping intracellular glucose concentration low — ensuring a continuous net inward flux. Without GLUT carriers, cells would be completely impermeable to glucose. Exception: intestines and kidney tubules use active transport for glucose absorption.
| Feature | Channel Proteins | Carrier Proteins |
|---|---|---|
| Mechanism | Hydrophilic pore/tunnel | Conformational shape change |
| Examples | Na⁺, K⁺, Cl⁻, Ca²⁺ | Glucose (GLUT transporters) |
| Gating | Ligand-gated or Voltage-gated | Substrate binding triggers change |
| Saturation | Less susceptible | Yes — saturates at max binding sites |
| Specificity | Ion-selective (one type of ion) | Highly specific to one substrate |
| ATP needed? | No | No |
Primary Active Transport
Sometimes cells must move particles uphill — against their concentration gradient. Primary active transport uses ATP directly to power protein pumps that do exactly this. The Na⁺/K⁺ ATPase pump is the most important example — it is present in every single cell and creates the electrochemical gradients that power nearly all cellular functions.
- Active transport moves particles against their concentration gradient (uphill)
- Primary active transport uses ATP directly — carrier proteins act as ATPases
- ATP is hydrolyzed → phosphorylation changes the pump protein shape
- Three main pumps: Na⁺/K⁺ ATPase, Ca²⁺ ATPase, H⁺ ATPase
- Na⁺/K⁺ pump: 3 Na⁺ out, 2 K⁺ in, 1 ATP per cycle — in ALL cells
- Electrogenic: 3 positive out vs 2 positive in → net negative charge inside
- Creates and maintains the resting membrane potential (−70 mV)
- Nerve cells spend 70% of their energy on this pump alone
- Ca²⁺ pump keeps intracellular Ca²⁺ critically low — essential for cell signaling
- H⁺ pump in stomach → secretion of hydrochloric acid (HCl)
- Without the Na⁺/K⁺ pump, nerve conduction, muscle contraction, and secondary transport all fail
- The Na⁺ gradient created by this pump also powers secondary active transport
- Blocking ATP synthesis stops primary active transport entirely
- Active transport proteins are always transmembrane and highly specific
The Na⁺/K⁺ pump is present in all cell membranes. It is a cotransport antiport system: it moves two different ions in opposite directions using one ATP per cycle. This pump creates the characteristic distribution of high intracellular K⁺ and low intracellular Na⁺ — the foundation of all electrical activity in cells.
| Ion | Inside Cell (ICF) | Outside Cell (ECF) | Maintained By |
|---|---|---|---|
| Na⁺ | ~15 mEq/L — LOW | ~142 mEq/L — HIGH | Na⁺/K⁺ pump pumps Na⁺ OUT |
| K⁺ | ~150 mEq/L — HIGH | ~5 mEq/L — LOW | Na⁺/K⁺ pump pumps K⁺ IN |
| Ca²⁺ | ~0.0001 mEq/L — VERY LOW | ~2.4 mEq/L — HIGH | Ca²⁺ ATPase pump |
The Na⁺/K⁺ pump exports 3 positive charges (Na⁺ out) but imports only 2 positive charges (K⁺ in). This unequal exchange generates a net negative charge inside the cell — a membrane potential. The pump is therefore called electrogenic. This electrical potential is the foundation of nerve impulses and muscle contraction.
| Pump | Location | Direction | Function |
|---|---|---|---|
| Na⁺/K⁺ ATPase | All cell membranes | 3 Na⁺ out · 2 K⁺ in | Membrane potential; drives secondary transport |
| Ca²⁺ ATPase | Plasma membrane, ER, mitochondria | Ca²⁺ out of cytoplasm | Keeps cytoplasmic Ca²⁺ extremely low for signaling |
| H⁺ ATPase | Plasma membrane, inner mitochondrial | H⁺ out of cells | Stomach HCl secretion; ATP synthesis in mitochondria |
Secondary Active Transport
Secondary active transport uses stored energy — specifically the Na⁺ gradient created by the Na⁺/K⁺ pump — rather than ATP directly. As Na⁺ flows inward (passively, down its gradient), it releases energy that drives a second molecule against its own gradient. This indirectly-powered cotransport is critical for nutrient absorption in the gut and kidney.
- Does not directly use ATP — uses the Na⁺ gradient as stored energy
- The Na⁺ gradient is created by the Na⁺/K⁺ pump (primary active transport)
- Always involves exactly 2 solutes transported together
- Na⁺ moves down its gradient (passively); energy released drives the second solute uphill
- Symport: both solutes move in the SAME direction (both into or both out of cell)
- Antiport: two solutes move in OPPOSITE directions
- Na⁺/glucose symport: absorption of glucose from intestines and kidney tubules
- Na⁺/amino acid symport: absorption of amino acids similarly
- Na⁺/Ca²⁺ antiport: helps keep cytoplasmic Ca²⁺ critically low
- All secondary active transport depends on primary active transport (Na⁺/K⁺ pump)
- If Na⁺/K⁺ pump fails, secondary transport fails too
- SGLT2 inhibitors (diabetes drugs) block Na⁺/glucose symport in the kidney
- Ca²⁺ uses both primary (Ca²⁺ ATPase) and secondary (Na⁺/Ca²⁺ antiport) to stay low
- Both Na⁺ and co-transported molecule move into the cell
- Na⁺/Glucose: powers glucose absorption in intestines and kidneys
- Na⁺/Amino acids: powers protein building-block absorption in gut
- Both are absorbed together through the intestinal epithelial cells into blood
- Na⁺ enters while another molecule is pumped out
- Na⁺/Ca²⁺ antiport: Na⁺ in → Ca²⁺ out
- Keeps intracellular Ca²⁺ extremely low for signaling
- Works alongside Ca²⁺ ATPase as a double backup system
SGLT2 (Sodium-Glucose Linked Transporter 2) is the Na⁺/glucose symporter in the kidney tubules. SGLT2 inhibitors (e.g., empagliflozin, dapagliflozin, canagliflozin) block this cotransporter, preventing glucose reabsorption from the kidney filtrate. Glucose is then excreted in the urine, lowering blood sugar levels. This is a direct clinical application of secondary active transport biology.
Vesicular Transport
Some molecules — large proteins, polysaccharides, even entire microorganisms — are far too large for any channel or carrier. Cells solve this by wrapping them in a membrane-bound vesicle. Exocytosis releases cargo outside the cell; endocytosis brings cargo in. Phagocytosis by white blood cells is your immune system in action.
- Large molecules cannot pass through channels or carriers
- Cells use membrane-bound vesicles for bulk transport
- Two main directions: out of cell (exocytosis) and into cell (endocytosis)
- Requires energy — membrane must be bent, pinched, and fused
- Exocytosis: vesicle fuses with plasma membrane → releases contents to ECF
- Endocytosis: plasma membrane cups around material → pinches off → vesicle forms inside
- Pinocytosis ("cell drinking"): small vesicles for fluid and dissolved solutes
- Phagocytosis ("cell eating"): large vesicles for bacteria, viruses, cellular debris
- Most cells do pinocytosis continuously; only WBCs (neutrophils, macrophages) do phagocytosis
- Insulin secretion by pancreatic beta cells uses exocytosis
- Phagocytosis by neutrophils and macrophages is the front line of immune defense
- Vesicular transport is also critical for intracellular organelle communication
- All membrane-enclosed cargo is isolated from the cytoplasm — no leakage
| Type | Common Name | Vesicle Size | Cargo Taken In | Which Cells |
|---|---|---|---|---|
| Pinocytosis | "Cellular Drinking" | Small | Extracellular fluid and dissolved solutes | Almost all eukaryotic cells — continuously |
| Phagocytosis | "Cellular Eating" | Large (phagosome) | Bacteria, viruses, damaged cell debris, foreign particles | Only neutrophils and macrophages (WBCs) |
Neutrophils and macrophages (white blood cells) use phagocytosis to engulf and destroy invading bacteria, viruses, and damaged cells. The engulfed material is enclosed in a phagosome that fuses with lysosomes — organelles containing digestive enzymes that break down the pathogen. This is the cellular basis of innate immune defense.
| Transport Type | Direction | ATP? | Protein Needed? | Example |
|---|---|---|---|---|
| Simple Diffusion | High → Low | No | No | O₂, CO₂, steroid hormones |
| Osmosis | High H₂O → Low H₂O | No | No (Aquaporins help) | Water across all membranes |
| Facilitated Diffusion | High → Low | No | Yes (channel/carrier) | Glucose (GLUT), Na⁺, K⁺ |
| Primary Active Transport | Low → High (against gradient) | Yes (direct) | Yes (pump/ATPase) | Na⁺/K⁺ pump, Ca²⁺ pump |
| Secondary Active Transport | Low → High (against gradient) | Indirect (Na⁺ gradient) | Yes (cotransporter) | Na⁺/glucose symport in gut |
| Exocytosis | Out of cell | Yes | Yes (SNARE proteins) | Insulin secretion |
| Endocytosis (Pinocytosis) | Into cell | Yes | Yes | Fluid uptake by all cells |
| Endocytosis (Phagocytosis) | Into cell | Yes | Yes | Bacteria engulfment by WBCs |