Cell Membrane and Transport

Membrane structure and mechanisms of transport across membranes

🧱 Cell Membrane and Transport

Fluid Mosaic Model

Structure:

Phospholipid bilayer forms foundation
Proteins embedded or attached
Cholesterol maintains fluidity
Carbohydrates attached (glycoproteins, glycolipids)

Properties:

Fluid: phospholipids and proteins can move laterally
Mosaic: varied composition of proteins and lipids
Selectively permeable: controls what enters/exits

Components:

Phospholipids:
- Hydrophilic heads face water
- Hydrophobic tails face each other
- Form bilayer spontaneously
Membrane proteins:
- Integral proteins: embedded in membrane (transmembrane)
- Peripheral proteins: attached to surface
Cholesterol:
- Maintains fluidity at different temperatures
- Prevents tight packing at low temps
- Restricts movement at high temps
Carbohydrates:
- Attached to proteins (glycoproteins)
- Attached to lipids (glycolipids)
- Cell recognition, adhesion

Transport Mechanisms

Passive Transport (No ATP required)

1. Simple Diffusion

Movement from high → low concentration
Down concentration gradient
Small, nonpolar molecules (O₂, CO₂)

2. Facilitated Diffusion

Uses membrane proteins
Down concentration gradient
Channel proteins: form pores (ions)
Carrier proteins: change shape (glucose)

3. Osmosis

Diffusion of water across membrane
Moves from high water → low water concentration
From low solute → high solute concentration

Water potential (Ψ):

Ψ = Ψₛ + Ψₚ
Ψₛ = solute potential (negative)
Ψₚ = pressure potential
Water moves from high → low Ψ

Tonicity:

Hypertonic: higher solute outside → cell shrinks (crenation/plasmolysis)
Hypotonic: lower solute outside → cell swells (lysis/turgid)
Isotonic: equal solute → no net movement

Active Transport (Requires ATP)

1. Primary Active Transport

Directly uses ATP
Moves against concentration gradient
Example: Na⁺/K⁺ pump
- Pumps 3 Na⁺ out, 2 K⁺ in
- Maintains concentration gradients

2. Secondary Active Transport

Uses electrochemical gradient
No direct ATP use
Cotransport: use one gradient to move another
- Symport: same direction
- Antiport: opposite directions

3. Bulk Transport

Endocytosis (into cell):

Phagocytosis: "cell eating" (solid particles)
Pinocytosis: "cell drinking" (fluid)
Receptor-mediated: specific molecules bind receptors

Exocytosis (out of cell):

Vesicles fuse with membrane
Release contents outside
Secretion of proteins, hormones

Key Concepts

Fluid mosaic model: phospholipid bilayer with proteins
Selectively permeable: controls what crosses
Passive transport: no energy, down gradient
Active transport: requires energy, against gradient
Osmosis: diffusion of water across membrane
Water moves from high → low water potential
Bulk transport: large molecules via vesicles

📚 Practice Problems

1Problem 1medium

❓ Question:

Compare and contrast the following transport mechanisms: (a) simple diffusion, (b) facilitated diffusion, and (c) active transport. Include examples and whether each requires energy.

💡 Show Solution

Membrane Transport Mechanisms:

(a) Simple Diffusion:

Mechanism:

Molecules move directly through lipid bilayer
Down concentration gradient (high → low)
No protein required

Requirements:

✗ No energy (ATP) needed - passive
✗ No transport protein needed
Molecules must be small and/or nonpolar

Rate factors:

Concentration gradient
Temperature
Molecular size
Lipid solubility

Examples:

O₂, CO₂ (respiratory gases)
N₂
Small nonpolar molecules (ethanol, glycerol)
Lipid-soluble substances (steroid hormones)

Equation (Fick's Law): $\text{Rate} \propto \frac{\Delta C \cdot A}{\Delta x}$

(b) Facilitated Diffusion:

Mechanism:

Molecules move through channel proteins or carrier proteins
Down concentration gradient (high → low)
Protein-mediated

Requirements:

✗ No energy (ATP) needed - passive
✓ Requires specific transport protein
Selective based on protein specificity

Types:

1. Channel proteins:

Aquaporins (water)
Ion channels (Na⁺, K⁺, Ca²⁺, Cl⁻)
Can be gated (open/close in response to signal)

2. Carrier proteins:

Bind substrate
Change conformation
Release on other side
Example: GLUT1 (glucose transporter)

Characteristics:

Shows saturation kinetics (max rate at high [S])
Specific for certain molecules
Faster than simple diffusion for large/polar molecules

Examples:

Glucose into cells (GLUT transporters)
Amino acids
Ions through channels
Water through aquaporins

(c) Active Transport:

Mechanism:

Molecules pumped against concentration gradient (low → high)
Requires energy input (ATP)
Uses carrier proteins (pumps)

Requirements:

✓ Energy (ATP) required - active
✓ Requires specific pump protein
Can create concentration gradients

Types:

1. Primary active transport:

ATP directly powers transport
Example: Na⁺/K⁺-ATPase pump
- 3 Na⁺ out, 2 K⁺ in
- Maintains electrochemical gradient
- ~30% of cell's ATP used!

2. Secondary active transport (cotransport):

Uses gradient created by primary transport
Symport: both move same direction (Na⁺-glucose)
Antiport: move opposite directions (Na⁺/Ca²⁺ exchanger)

Examples:

Na⁺/K⁺ pump (all animal cells)
Ca²⁺ pumps (muscle cells)
H⁺ pumps (stomach acid, plant roots)
Na⁺-glucose cotransporter (intestine)

Comparison Table:

| Feature | Simple Diffusion | Facilitated Diffusion | Active Transport | |---------|------------------|----------------------|------------------| | Energy? | No (passive) | No (passive) | Yes (ATP) | | Protein? | No | Yes | Yes | | Direction | Down gradient | Down gradient | Against gradient | | Saturation? | No | Yes | Yes | | Examples | O₂, CO₂ | Glucose, ions (channels) | Na⁺/K⁺ pump | | Speed | Slow for large/polar | Faster than simple | Variable |

$\boxed{\text{Passive (down gradient): simple/facilitated; Active (against gradient): requires ATP}}$

Energetics:

Passive: $\Delta G < 0$ (spontaneous)
Active: $\Delta G > 0$ (requires energy input from ATP hydrolysis)

2Problem 2medium

❓ Question:

Compare and contrast the following transport mechanisms: (a) simple diffusion, (b) facilitated diffusion, and (c) active transport. Include examples and whether each requires energy.

💡 Show Solution

Membrane Transport Mechanisms:

(a) Simple Diffusion:

Mechanism:

Molecules move directly through lipid bilayer
Down concentration gradient (high → low)
No protein required

Requirements:

✗ No energy (ATP) needed - passive
✗ No transport protein needed
Molecules must be small and/or nonpolar

Rate factors:

Concentration gradient
Temperature
Molecular size
Lipid solubility

Examples:

O₂, CO₂ (respiratory gases)
N₂
Small nonpolar molecules (ethanol, glycerol)
Lipid-soluble substances (steroid hormones)

Equation (Fick's Law): $\text{Rate} \propto \frac{\Delta C \cdot A}{\Delta x}$

(b) Facilitated Diffusion:

Mechanism:

Molecules move through channel proteins or carrier proteins
Down concentration gradient (high → low)
Protein-mediated

Requirements:

✗ No energy (ATP) needed - passive
✓ Requires specific transport protein
Selective based on protein specificity

Types:

1. Channel proteins:

Aquaporins (water)
Ion channels (Na⁺, K⁺, Ca²⁺, Cl⁻)
Can be gated (open/close in response to signal)

2. Carrier proteins:

Bind substrate
Change conformation
Release on other side
Example: GLUT1 (glucose transporter)

Characteristics:

Shows saturation kinetics (max rate at high [S])
Specific for certain molecules
Faster than simple diffusion for large/polar molecules

Examples:

Glucose into cells (GLUT transporters)
Amino acids
Ions through channels
Water through aquaporins

(c) Active Transport:

Mechanism:

Molecules pumped against concentration gradient (low → high)
Requires energy input (ATP)
Uses carrier proteins (pumps)

Requirements:

✓ Energy (ATP) required - active
✓ Requires specific pump protein
Can create concentration gradients

Types:

1. Primary active transport:

ATP directly powers transport
Example: Na⁺/K⁺-ATPase pump
- 3 Na⁺ out, 2 K⁺ in
- Maintains electrochemical gradient
- ~30% of cell's ATP used!

2. Secondary active transport (cotransport):

Uses gradient created by primary transport
Symport: both move same direction (Na⁺-glucose)
Antiport: move opposite directions (Na⁺/Ca²⁺ exchanger)

Examples:

Na⁺/K⁺ pump (all animal cells)
Ca²⁺ pumps (muscle cells)
H⁺ pumps (stomach acid, plant roots)
Na⁺-glucose cotransporter (intestine)

Comparison Table:

$\boxed{\text{Passive (down gradient): simple/facilitated; Active (against gradient): requires ATP}}$

Energetics:

Passive: $\Delta G < 0$ (spontaneous)
Active: $\Delta G > 0$ (requires energy input from ATP hydrolysis)

3Problem 3medium

❓ Question:

Compare and contrast the following transport mechanisms: (a) simple diffusion, (b) facilitated diffusion, and (c) active transport. Include examples and whether each requires energy.

💡 Show Solution

Membrane Transport Mechanisms:

(a) Simple Diffusion:

Mechanism:

Molecules move directly through lipid bilayer
Down concentration gradient (high → low)
No protein required

Requirements:

✗ No energy (ATP) needed - passive
✗ No transport protein needed
Molecules must be small and/or nonpolar

Rate factors:

Concentration gradient
Temperature
Molecular size
Lipid solubility

Examples:

O₂, CO₂ (respiratory gases)
N₂
Small nonpolar molecules (ethanol, glycerol)
Lipid-soluble substances (steroid hormones)

Equation (Fick's Law): $\text{Rate} \propto \frac{\Delta C \cdot A}{\Delta x}$

(b) Facilitated Diffusion:

Mechanism:

Molecules move through channel proteins or carrier proteins
Down concentration gradient (high → low)
Protein-mediated

Requirements:

✗ No energy (ATP) needed - passive
✓ Requires specific transport protein
Selective based on protein specificity

Types:

1. Channel proteins:

Aquaporins (water)
Ion channels (Na⁺, K⁺, Ca²⁺, Cl⁻)
Can be gated (open/close in response to signal)

2. Carrier proteins:

Bind substrate
Change conformation
Release on other side
Example: GLUT1 (glucose transporter)

Characteristics:

Shows saturation kinetics (max rate at high [S])
Specific for certain molecules
Faster than simple diffusion for large/polar molecules

Examples:

Glucose into cells (GLUT transporters)
Amino acids
Ions through channels
Water through aquaporins

(c) Active Transport:

Mechanism:

Molecules pumped against concentration gradient (low → high)
Requires energy input (ATP)
Uses carrier proteins (pumps)

Requirements:

✓ Energy (ATP) required - active
✓ Requires specific pump protein
Can create concentration gradients

Types:

1. Primary active transport:

ATP directly powers transport
Example: Na⁺/K⁺-ATPase pump
- 3 Na⁺ out, 2 K⁺ in
- Maintains electrochemical gradient
- ~30% of cell's ATP used!

2. Secondary active transport (cotransport):

Uses gradient created by primary transport
Symport: both move same direction (Na⁺-glucose)
Antiport: move opposite directions (Na⁺/Ca²⁺ exchanger)

Examples:

Na⁺/K⁺ pump (all animal cells)
Ca²⁺ pumps (muscle cells)
H⁺ pumps (stomach acid, plant roots)
Na⁺-glucose cotransporter (intestine)

Comparison Table:

$\boxed{\text{Passive (down gradient): simple/facilitated; Active (against gradient): requires ATP}}$

Energetics:

Passive: $\Delta G < 0$ (spontaneous)
Active: $\Delta G > 0$ (requires energy input from ATP hydrolysis)

4Problem 4hard

❓ Question:

Explain how the Na⁺/K⁺-ATPase pump works: (a) describe the step-by-step mechanism, (b) explain why this is electrogenic, and (c) discuss how this pump enables secondary active transport (use glucose absorption as an example).

💡 Show Solution

Na⁺/K⁺-ATPase Pump:

(a) Step-by-step mechanism:

Cycle has 6 main steps:

Step 1: Binding (Cytoplasmic side)

3 Na⁺ ions bind to pump from inside cell
Pump in "E₁" conformation (open to cytoplasm)
High affinity for Na⁺ in this state

Step 2: Phosphorylation

ATP binds to pump
ATP hydrolyzed: ATP → ADP + Pi
Phosphate (Pi) covalently attached to aspartate residue
Pump now "energized"

$\text{E}_1\text{-ATP} \rightarrow \text{E}_1\text{-P} + \text{ADP}$

Step 3: Conformational change

Phosphorylation causes shape change
Pump switches to "E₂" conformation (open to extracellular)
Na⁺ binding sites now face outside
Affinity for Na⁺ decreases

Step 4: Na⁺ release

3 Na⁺ released to extracellular fluid
Pump still phosphorylated

Step 5: K⁺ binding

2 K⁺ bind from outside
E₂ conformation has high affinity for K⁺
K⁺ binding triggers dephosphorylation

Step 6: Dephosphorylation and return

Phosphate released from pump
Pump returns to E₁ conformation
K⁺ binding sites now face cytoplasm
Affinity for K⁺ decreases
2 K⁺ released into cytoplasm
Cycle repeats

Net Result: $\text{3 Na}^+ \text{ (out)} + \text{2 K}^+ \text{ (in)} + \text{ATP} \rightarrow \text{3 Na}^+ \text{ (out)} + \text{2 K}^+ \text{ (in)} + \text{ADP} + \text{P}_i$

(b) Why is this electrogenic?

Electrogenic = generates electrical potential

Charge imbalance:

3 positive charges (Na⁺) pumped OUT
2 positive charges (K⁺) pumped IN
Net: 1 positive charge removed per cycle

Result:

Creates membrane potential
Inside becomes more negative relative to outside
Typical: -70 mV (inside negative)

Contribution to resting potential:

Direct: ~-10 mV from pump itself
Indirect: ~-60 mV from K⁺ leak channels (enabled by gradient)
Total: ~-70 mV

$\Delta V = \frac{RT}{F}\ln\frac{[K^+]_{out}}{[K^+]_{in}}$

(c) Secondary active transport - glucose absorption:

Primary transport creates gradient:

Na⁺/K⁺ pump → low [Na⁺] inside, high [Na⁺] outside

Secondary transport exploits gradient:

SGLT1 (Sodium-Glucose Linked Transporter) in intestinal epithelium:

Mechanism:

SGLT1 binds 2 Na⁺ + 1 glucose from intestinal lumen
Na⁺ moving down gradient (high → low) provides energy
Energy used to move glucose against its gradient (low → high)
Both released into cytoplasm

This is SYMPORT (both move same direction)

Energy source:

NOT directly ATP
Uses Na⁺ gradient (created by Na⁺/K⁺ pump using ATP)
Indirect use of ATP

Complete pathway for glucose absorption:

Intestinal Lumen → Epithelial Cell → Blood

Step 1: SGLT1 (apical membrane)
   Glucose + 2Na⁺  →  into cell
   (secondary active, symport)

Step 2: GLUT2 (basolateral membrane)
   Glucose  →  out to blood
   (facilitated diffusion, down gradient)

Step 3: Na⁺/K⁺ pump (basolateral membrane)
   Maintains low [Na⁺] inside
   (primary active transport)

Why this works:

Na⁺ gradient provides "free" energy for glucose transport
One ATP → multiple glucose molecules transported
More efficient than direct ATP use for each glucose

Energetics:

Primary active: $\Delta G_{ATP} = -30.5$ kJ/mol Drives: [Na⁺] gradient = +10-12 kJ/mol Used for: glucose uptake against gradient = +5-8 kJ/mol

$\boxed{\text{Pump creates Na}^+ \text{ gradient → SGLT1 uses gradient → glucose absorbed}}$

Clinical relevance:

Oral rehydration therapy (ORT) uses this!
Na⁺ + glucose solution
Glucose absorption drives Na⁺ and water absorption
Treats dehydration from diarrhea

5Problem 5hard

❓ Question:

💡 Show Solution

Na⁺/K⁺-ATPase Pump:

(a) Step-by-step mechanism:

Cycle has 6 main steps:

Step 1: Binding (Cytoplasmic side)

3 Na⁺ ions bind to pump from inside cell
Pump in "E₁" conformation (open to cytoplasm)
High affinity for Na⁺ in this state

Step 2: Phosphorylation

ATP binds to pump
ATP hydrolyzed: ATP → ADP + Pi
Phosphate (Pi) covalently attached to aspartate residue
Pump now "energized"

$\text{E}_1\text{-ATP} \rightarrow \text{E}_1\text{-P} + \text{ADP}$

Step 3: Conformational change

Phosphorylation causes shape change
Pump switches to "E₂" conformation (open to extracellular)
Na⁺ binding sites now face outside
Affinity for Na⁺ decreases

Step 4: Na⁺ release

3 Na⁺ released to extracellular fluid
Pump still phosphorylated

Step 5: K⁺ binding

2 K⁺ bind from outside
E₂ conformation has high affinity for K⁺
K⁺ binding triggers dephosphorylation

Step 6: Dephosphorylation and return

Phosphate released from pump
Pump returns to E₁ conformation
K⁺ binding sites now face cytoplasm
Affinity for K⁺ decreases
2 K⁺ released into cytoplasm
Cycle repeats

Net Result: $\text{3 Na}^+ \text{ (out)} + \text{2 K}^+ \text{ (in)} + \text{ATP} \rightarrow \text{3 Na}^+ \text{ (out)} + \text{2 K}^+ \text{ (in)} + \text{ADP} + \text{P}_i$

(b) Why is this electrogenic?

Electrogenic = generates electrical potential

Charge imbalance:

3 positive charges (Na⁺) pumped OUT
2 positive charges (K⁺) pumped IN
Net: 1 positive charge removed per cycle

Result:

Creates membrane potential
Inside becomes more negative relative to outside
Typical: -70 mV (inside negative)

Contribution to resting potential:

Direct: ~-10 mV from pump itself
Indirect: ~-60 mV from K⁺ leak channels (enabled by gradient)
Total: ~-70 mV

$\Delta V = \frac{RT}{F}\ln\frac{[K^+]_{out}}{[K^+]_{in}}$

(c) Secondary active transport - glucose absorption:

Primary transport creates gradient:

Na⁺/K⁺ pump → low [Na⁺] inside, high [Na⁺] outside

Secondary transport exploits gradient:

SGLT1 (Sodium-Glucose Linked Transporter) in intestinal epithelium:

Mechanism:

SGLT1 binds 2 Na⁺ + 1 glucose from intestinal lumen
Na⁺ moving down gradient (high → low) provides energy
Energy used to move glucose against its gradient (low → high)
Both released into cytoplasm

This is SYMPORT (both move same direction)

Energy source:

NOT directly ATP
Uses Na⁺ gradient (created by Na⁺/K⁺ pump using ATP)
Indirect use of ATP

Complete pathway for glucose absorption:

Intestinal Lumen → Epithelial Cell → Blood

Step 1: SGLT1 (apical membrane)
   Glucose + 2Na⁺  →  into cell
   (secondary active, symport)

Step 2: GLUT2 (basolateral membrane)
   Glucose  →  out to blood
   (facilitated diffusion, down gradient)

Step 3: Na⁺/K⁺ pump (basolateral membrane)
   Maintains low [Na⁺] inside
   (primary active transport)

Why this works:

Na⁺ gradient provides "free" energy for glucose transport
One ATP → multiple glucose molecules transported
More efficient than direct ATP use for each glucose

Energetics:

Primary active: $\Delta G_{ATP} = -30.5$ kJ/mol Drives: [Na⁺] gradient = +10-12 kJ/mol Used for: glucose uptake against gradient = +5-8 kJ/mol

$\boxed{\text{Pump creates Na}^+ \text{ gradient → SGLT1 uses gradient → glucose absorbed}}$

Clinical relevance:

Oral rehydration therapy (ORT) uses this!
Na⁺ + glucose solution
Glucose absorption drives Na⁺ and water absorption
Treats dehydration from diarrhea

6Problem 6hard

❓ Question:

💡 Show Solution

Na⁺/K⁺-ATPase Pump:

(a) Step-by-step mechanism:

Cycle has 6 main steps:

Step 1: Binding (Cytoplasmic side)

3 Na⁺ ions bind to pump from inside cell
Pump in "E₁" conformation (open to cytoplasm)
High affinity for Na⁺ in this state

Step 2: Phosphorylation

ATP binds to pump
ATP hydrolyzed: ATP → ADP + Pi
Phosphate (Pi) covalently attached to aspartate residue
Pump now "energized"

$\text{E}_1\text{-ATP} \rightarrow \text{E}_1\text{-P} + \text{ADP}$

Step 3: Conformational change

Phosphorylation causes shape change
Pump switches to "E₂" conformation (open to extracellular)
Na⁺ binding sites now face outside
Affinity for Na⁺ decreases

Step 4: Na⁺ release

3 Na⁺ released to extracellular fluid
Pump still phosphorylated

Step 5: K⁺ binding

2 K⁺ bind from outside
E₂ conformation has high affinity for K⁺
K⁺ binding triggers dephosphorylation

Step 6: Dephosphorylation and return

Phosphate released from pump
Pump returns to E₁ conformation
K⁺ binding sites now face cytoplasm
Affinity for K⁺ decreases
2 K⁺ released into cytoplasm
Cycle repeats

Net Result: $\text{3 Na}^+ \text{ (out)} + \text{2 K}^+ \text{ (in)} + \text{ATP} \rightarrow \text{3 Na}^+ \text{ (out)} + \text{2 K}^+ \text{ (in)} + \text{ADP} + \text{P}_i$

(b) Why is this electrogenic?

Electrogenic = generates electrical potential

Charge imbalance:

3 positive charges (Na⁺) pumped OUT
2 positive charges (K⁺) pumped IN
Net: 1 positive charge removed per cycle

Result:

Creates membrane potential
Inside becomes more negative relative to outside
Typical: -70 mV (inside negative)

Contribution to resting potential:

Direct: ~-10 mV from pump itself
Indirect: ~-60 mV from K⁺ leak channels (enabled by gradient)
Total: ~-70 mV

$\Delta V = \frac{RT}{F}\ln\frac{[K^+]_{out}}{[K^+]_{in}}$

(c) Secondary active transport - glucose absorption:

Primary transport creates gradient:

Na⁺/K⁺ pump → low [Na⁺] inside, high [Na⁺] outside

Secondary transport exploits gradient:

SGLT1 (Sodium-Glucose Linked Transporter) in intestinal epithelium:

Mechanism:

SGLT1 binds 2 Na⁺ + 1 glucose from intestinal lumen
Na⁺ moving down gradient (high → low) provides energy
Energy used to move glucose against its gradient (low → high)
Both released into cytoplasm

This is SYMPORT (both move same direction)

Energy source:

NOT directly ATP
Uses Na⁺ gradient (created by Na⁺/K⁺ pump using ATP)
Indirect use of ATP

Complete pathway for glucose absorption:

Intestinal Lumen → Epithelial Cell → Blood

Step 1: SGLT1 (apical membrane)
   Glucose + 2Na⁺  →  into cell
   (secondary active, symport)

Step 2: GLUT2 (basolateral membrane)
   Glucose  →  out to blood
   (facilitated diffusion, down gradient)

Step 3: Na⁺/K⁺ pump (basolateral membrane)
   Maintains low [Na⁺] inside
   (primary active transport)

Why this works:

Na⁺ gradient provides "free" energy for glucose transport
One ATP → multiple glucose molecules transported
More efficient than direct ATP use for each glucose

Energetics:

Primary active: $\Delta G_{ATP} = -30.5$ kJ/mol Drives: [Na⁺] gradient = +10-12 kJ/mol Used for: glucose uptake against gradient = +5-8 kJ/mol

$\boxed{\text{Pump creates Na}^+ \text{ gradient → SGLT1 uses gradient → glucose absorbed}}$

Clinical relevance:

Oral rehydration therapy (ORT) uses this!
Na⁺ + glucose solution
Glucose absorption drives Na⁺ and water absorption
Treats dehydration from diarrhea

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