Movement of Substances Through Membranes

💨

Simple Diffusion

Passive · No proteins needed · Down gradient

▼

①

Concentration Gradient Exists

Particles accumulate at higher concentration on one side of the membrane. This gradient is the driving force — no ATP needed.

②

Kinetic Energy Drives Movement

Above 0 K (absolute zero), all molecules have kinetic energy from heat. They move randomly but net movement is always from high → low concentration.

③

Molecule Crosses Lipid Bilayer

Only small, hydrophobic, non-polar molecules pass directly. Examples: O₂, CO₂, fatty acids, steroid hormones (testosterone, estrogen).

O₂ CO₂ Fatty Acids Steroids

④

Equilibrium Reached

Net movement stops when concentrations equalize on both sides. Molecules still move, but equally in both directions.

⚡ Factors that Speed Up Diffusion

↑ Temperature · ↓ Molecular size & mass · Less dense medium · Steeper concentration gradient · Higher lipid solubility of molecule

💧

Osmosis

Water diffusion · Semipermeable membrane

▼

①

Two Compartments Separated by Semipermeable Membrane

One side has higher solute concentration (lower water concentration). The membrane allows only water to pass freely.

②

Net Water Movement

Water moves from the dilute side (high H₂O) to the concentrated side (low H₂O) — always following its own concentration gradient.

③

Osmotic Pressure Builds

The pressure required to stop osmotic flow equals the osmotic pressure. Higher osmolarity = higher osmotic pressure = more tendency to draw water in.

🔬 Osmolarity — Key Concept

Total solute concentration in osmoles/L.
• 1M Glucose = 1 osmol/L
• 1M NaCl = 2 osmol/L (dissociates into Na⁺ + Cl⁻)
• 1M MgCl₂ = 3 osmol/L (Mg²⁺ + 2Cl⁻)

Solution Type	Cell Behavior	Net Water Flow
Isotonic	Normal shape	None (balanced)
Hypotonic	Cell swells/lyses	Into cell
Hypertonic	Cell shrinks (crenates)	Out of cell

🚪

Facilitated Diffusion

Protein-assisted · Passive · Down gradient

▼

Why is it needed?

Charged ions (Na⁺, K⁺, Cl⁻) and large polar molecules (glucose) cannot cross the hydrophobic lipid bilayer. Membrane proteins act as selective gates.

🔓 Channel-Mediated Diffusion ▼

①

Channel Protein Spans Membrane

Transmembrane proteins form a hydrophilic tunnel. Each channel is selective — specific ions only (Na⁺, K⁺, Ca²⁺, Cl⁻).

②

Channel Opens via Stimulus

Channels are normally closed. They open when triggered by:
• Ligand-gating: binding of a molecule (e.g. acetylcholine)
• Voltage-gating: change in membrane potential

③

Ion Flows Down Gradient

Both concentration gradient and electric force drive movement. Ions move passively — no energy consumed.

🔄 Carrier-Mediated Diffusion ▼

①

Molecule Binds to Carrier Protein

Substance (e.g. glucose) binds to a specific binding site on one side of the carrier protein. Shape-lock fit — highly selective.

②

Conformational Change (No ATP)

The protein changes shape, flipping the binding site to the opposite membrane surface. This does NOT require ATP energy.

③

Molecule Released

Substance dissociates. Carrier returns to original shape. Process can saturate when all carrier sites are occupied.

Key Example

Glucose transport — without carriers, cells are impermeable to glucose. GLUT transporters move glucose into most body cells by carrier-mediated diffusion.

⚡

Primary Active Transport

ATP-powered · Against gradient · Protein pumps

▼

Core Principle

Moves particles AGAINST their concentration gradient (low → high). Requires direct ATP hydrolysis to power protein pumps.

🔋 Na⁺/K⁺ Pump (Na⁺/K⁺ ATPase) — Most Important ▼

①

ATP Hydrolysis

ATP is hydrolyzed → ADP + Pᵢ. The phosphate group phosphorylates the pump protein, activating it.

②

3 Na⁺ Pumped OUT

Three sodium ions (Na⁺) are expelled from the cytoplasm to the extracellular fluid — against their gradient.

③

2 K⁺ Pumped IN

Two potassium ions (K⁺) enter the cell from the extracellular fluid — also against their gradient.

④

Net Charge Imbalance Created

Electrogenic pump: 3+ out vs 2+ in = net negative charge inside cell. This maintains the resting membrane potential (~−70 mV).

Antiport Electrogenic Every cell

🦴 Ca²⁺ Pump (Ca²⁺ ATPase) ▼

Located in plasma membrane, ER, and mitochondria. Pumps Ca²⁺ out of the cytoplasm, maintaining very low intracellular Ca²⁺ concentration. Critical for muscle contraction signaling and cell signaling pathways.

🔬 H⁺ Pump (H⁺ ATPase) ▼

Found in plasma membrane and inner mitochondrial membrane. Pumps H⁺ (protons) out of cells. Crucial for ATP synthesis in mitochondria (proton-motive force) and gastric acid secretion.

🔗

Secondary Active Transport

Na⁺ gradient powered · Indirect ATP use

▼

①

Na⁺ Gradient Pre-established

The Na⁺/K⁺ pump (primary active transport) creates a steep Na⁺ gradient — high outside, low inside. This stored energy powers secondary transport.

②

Cotransporter Protein Binds Both Molecules

A cotransporter simultaneously binds Na⁺ (moving down its gradient) AND a second molecule (e.g. glucose) that needs to go against its gradient.

③

Na⁺ Energy Drives Both Molecules

Na⁺ "falls" into the cell energetically, and this energy is harnessed to pull the second molecule along — against its concentration gradient.

④

Both Released Inside Cell

Na⁺ and the co-transported molecule enter the cytoplasm. Na⁺ is later re-expelled by the Na⁺/K⁺ pump (consuming ATP indirectly).

Type	Direction	Example
Symport	Same direction ↓↓	Na⁺/Glucose, Na⁺/Amino acid
Antiport	Opposite directions ↑↓	Na⁺/Ca²⁺ exchanger

🏥 Clinical Relevance

Glucose absorption in intestines and kidney tubules uses Na⁺/glucose symport. SGLT2 inhibitors (diabetes drugs) block this system to reduce blood glucose.

📦

Vesicular Transport

Bulk transport · Large molecules · Membrane fusion

▼

Why Vesicles?

Large molecules (proteins, polysaccharides, lipid complexes) are too big for any channel or carrier. They are packaged into membrane-bound vesicles for transport.

📤 Exocytosis (OUT of cell) ▼

①

Molecule Packaged in Vesicle

e.g. Insulin is packaged into secretory vesicles inside the cell.

②

Vesicle Migrates to Membrane

Transported along cytoskeletal tracks to the plasma membrane.

③

Membrane Fusion & Release

Vesicle fuses with plasma membrane, opening to the extracellular space and releasing contents.

📥 Endocytosis (INTO cell) ▼

①

Plasma Membrane Engulfs Substance

A small region of plasma membrane surrounds extracellular material.

②

Membrane Pinches Off

Forms an intracellular vesicle containing the ingested material.

Type	Cargo	Vesicle Size
Pinocytosis	Fluid & small solutes	Small ("cell drinking")
Phagocytosis	Large particles, bacteria	Large ("cell eating")

Mechanism	Energy?	Direction	Proteins?	Examples
Simple Diffusion	❌ None	High → Low	None	O₂, CO₂, steroids
Osmosis	❌ None	High H₂O → Low H₂O	None	Water across membranes
Channel Diffusion	❌ None	High → Low	✅ Channel proteins	Na⁺, K⁺, Cl⁻, Ca²⁺
Carrier Diffusion	❌ None	High → Low	✅ Carrier proteins	Glucose (GLUT)
Primary Active	✅ ATP direct	Low → High	✅ Pumps (ATPase)	Na⁺/K⁺, Ca²⁺, H⁺ pumps
Secondary Active	✅ ATP indirect (Na⁺ gradient)	Low → High (cargo)	✅ Cotransporters	Na⁺/glucose symport
Exocytosis	✅ ATP	Out of cell	✅ Vesicles	Insulin secretion
Endocytosis	✅ ATP	Into cell	✅ Vesicles	Phagocytosis, pinocytosis