Chapter 5: Membranes - Biochemistry and Cell Biology

Reference and Introduction

• Textbook Reference: Mason K, Duncan T and Losos J. Understanding Biology, 3rd Edition (2021) McGraw-Hill. Chapter 5: Membranes.

• Course Code: SP CLS07 / CP2318 (Biochemistry & Cell Biology).

• Lesson Duration: 90 minutes.

General Structure of the Cell Membrane

The cell membrane is composed of four major structural components:

• Phospholipid Bilayer: The basic, foundational structure of every cell membrane. It forms a barrier to polar molecules while allowing non-polar molecules to diffuse freely.

• Transmembrane Proteins: Integral proteins that protrude through the plasma membrane. They possess non-polar regions that tether them to the hydrophobic interior of the membrane.

• Interior Protein Network: Inside the cell, membrane proteins interact with actin filaments and intermediate filaments.

• Cell Surface Markers: Carbohydrate chains are often bound to the extracellular portion of proteins, forming glycoproteins. Membrane phospholipids can also be modified with carbohydrates to form glycolipids. Animal cells typically possess an elaborate extracellular matrix (ECM) composed primarily of glycoproteins.

The Phospholipid Bilayer

• Structural Composition:

  • Glycerol: A 3-carbon polyalcohol.

  • Two Fatty Acids: Non-polar and hydrophobic ("water-fearing") tails attached to the glycerol.

  • Phosphate Group: A polar and hydrophilic ("water-loving") head attached to the glycerol.

• Amphipathic Nature: Phospholipids are amphipathic because they contain both polar (head) and non-polar (tail) regions.

• Spontaneous Formation: Bilayers form spontaneously in water, driven by the tendency of water molecules to form the maximum number of hydrogen bonds.

• Bilayer Orientation: Two layers of phospholipids arrange themselves with the non-polar ends facing each other in the interior and the polar hydrophilic heads facing the exterior environments.

• Example Phospholipid: Phosphatidylcholine.

The Fluid Mosaic Model

• Mosaic Nature: The phospholipid bilayer is embedded with proteins, creating a mosaic pattern.

• Fluid Nature: Phospholipids interact relatively weakly with one another. Individual phospholipids and unanchored proteins are free to move laterally within the membrane.

• Alterations in Fluidity:

  • Fatty Acid Composition: The presence of unsaturated fatty acids increases membrane fluidity.

  • Cholesterol: In animal cells, cholesterol acts as a stabilizer. It can increase the strength of the membrane but also decrease overall fluidity. In the outer leaflet of animal cells, cholesterol can make up as much as $50\%$ of membrane lipids.

Membrane Proteins: Types and Functions

Membrane proteins are divided into two primary categories based on their relationship with the bilayer:

1. Integral Membrane Proteins: Proteins embedded within the lipid membrane.

2. Peripheral Membrane Proteins: Proteins associated with the surface of the membrane.

Key Functions of Membrane Proteins:

• Transporters: Examples include ion channels of the plasma membrane.

• Enzymes: Examples include electron transport chains located in the inner mitochondrial membrane.

• Cell Surface Receptors: Examples include Receptor Tyrosine Kinase (RTK) and G Protein-Coupled Receptors (GPCR).

• Cell Surface Identity Markers: Examples include glycoproteins that identify the cell type.

• Cell to Cell Adhesion Proteins: Examples include cadherin.

• Cytoskeleton Anchors: Provide structural stability by anchoring to internal filaments.

Transmembrane Domains and Protein Structure

Transmembrane proteins are a specific type of integral protein that span the entire membrane. They typically consist of three domains:

• Extracellular Domain: Found outside the cell; often contains polar or charged amino acids.

• Transmembrane Domain: Found within the hydrophobic interior of the phospholipid bilayer. These domains consist primarily of non-polar amino acids. A protein may have a single transmembrane domain (e.g., cadherin) or multiple domains (e.g., GPCR with seven transmembrane domains).

• Intracellular (Cytoplasmic) Domain: Found in the cytoplasm; often contains polar or charged amino acids.

Movement of Substances Across Cell Membranes

There are three basic mechanisms for transport:

• Passive Transport: Movement down a concentration gradient; requires no energy. Examples: Diffusion, Facilitated Diffusion (via ion channels or carrier proteins), and Osmosis.

• Active Transport: Movement against a concentration gradient; requires energy (ATP). Examples: Sodium-Potassium ($Na^+ - K^+$) Pump, Coupled transport.

• Bulk Transport: Movement of large particles or volumes; requires energy. Examples: Endocytosis (Phagocytosis, Pinocytosis, Receptor-mediated) and Exocytosis.

Passive Transport: Simple and Facilitated Diffusion

• Simple Diffusion:

  • Movement from high concentration to low concentration.

  • Requires no energy.

  • Continues until concentration is uniform.

  • Limited to oxygen and non-polar molecules like steroid hormones.

• Facilitated Diffusion:

  • Required for polar molecules or ions that cannot cross the bilayer naturally.

  • Moves down a concentration gradient using proteins.

• Mechanisms of Facilitated Diffusion:

  1. Ion Channels: These possess a hydrated interior. Some are gated channels that open or close in response to electrical or chemical stimuli. They are specific to ions like $Ca^{2+}$, $Na^+$, $K^+$, or $Cl^-$.

  2. Carrier Proteins: These bind specifically to the molecules they transport (e.g., sugars, amino acids). They undergo a shape change to move the molecule across. The rate of transport is limited by the number of transporters and can become saturated.

Osmosis and Osmotic Concentration

• Definition: The net diffusion of water across a membrane toward a higher solute concentration.

• Mechanism: Water molecules form hydration shells around charged or polar solutes. This reduces the number of "free" water molecules. Water moves down its own concentration gradient (from low solute concentration to high solute concentration).

• Aquaporins: Specialized water protein channels that facilitate osmosis.

• Terminology:

  • Osmotic Concentration: Determined by the total concentration of all solutes in a solution.

  • Hypertonic: Solution with a higher osmotic concentration (water leaves the cell; cell shrivels).

  • Hypotonic: Solution with a lower osmotic concentration (water enters the cell; cell may rupture).

  • Isotonic: Solution with the same osmotic concentration; no net movement of water.

• Osmotic Pressure: The force needed to stop osmosis. Plant cells use strong cell walls to withstand hydrostatic pressure, preventing rupture.

Active Transport and Carrier Types

Active transport involves highly selective protein carriers that bind to substances to move them against their concentration gradient using ATP.

• Carrier Types:

  • Uniporters: Transport a single type of molecule.

  • Symporters: Transport two different substances in the same direction.

  • Antiporters: Transport two different substances in opposite directions.

The Sodium-Potassium ($Na^+ - K^+$) Pump

This is an antiporter mechanism essential for maintaining cellular ion concentrations (Low internal $Na^+$, High internal $K^+$).

The Cycle of the Pump:

1. Three $Na^+$ ions bind to the cytoplasmic side of the protein, inducing a conformation change.

2. The protein binds ATP and cleaves it into ADP and Phosphate ($P_i$). ADP is released.

3. The protein becomes phosphorylated ($P_i$ is covalently linked).

4. Phosphorylation induces a second conformational change, translocating the three $Na^+$ to the exterior.

5. The protein loses affinity for $Na^+$, and they dissociate into the extracellular fluid.

6. The new conformation has a high affinity for $K^+$. Two $K^+$ ions bind from the extracellular side.

7. Binding of $K^+$ causes the hydrolysis and release of the bound phosphate group.

8. The protein reverts to its original shape, exposing $K^+$ to the cytoplasm.

9. The protein loses affinity for $K^+$, and the ions dissociate into the interior. The high affinity for $Na^+$ returns to restart the cycle.

Coupled Transport

• Mechanism: Uses the energy released as one molecule moves down its concentration gradient to move a second molecule against its gradient.

• Example: Active transport of glucose via a Symporter.

• The symporter uses the $Na^+$ gradient maintained by the Sodium-Potassium pump. As $Na^+$ moves into the cell down its gradient, it carries a glucose molecule against its gradient.

Bulk Transport: Endocytosis and Exocytosis

• Endocytosis: Movement of substances into the cell via the plasma membrane enveloping particles.

  • Phagocytosis: Taking in particulate matter ("cell eating").

  • Pinocytosis: Taking in fluid ("cell drinking").

  • Receptor-Mediated Endocytosis: Specific molecules bind to cell surface receptors. The process involves pits coated with the protein clathrin. Example: Intake of cholesterol via LDL receptors.

• Exocytosis: Movement of substances out of the cell.

  • Molecules are secreted in vesicles that fuse with the plasma membrane.

  • Examples: Secretion of hormones and digestive enzymes.

Quiz and Review Points

• A phospholipid molecule consists of 1 glycerol, 2 fatty acids, and 1 phosphate group.

• Increasing cholesterol or decreasing unsaturated fatty acids can decrease membrane fluidity.

• Diffusion requires no energy and moves down a concentration gradient.

• Facilitated transport via ion channels/carriers is still considered passive transport.

• The Sodium-Potassium pump is an antiporter.

• Pinocytosis is a form of bulk transport/endocytosis involving fluid intake.

• Higher osmotic concentration = Hypertonic; Lower = Hypotonic; Same = Isotonic.

• Transmembrane proteins can have multiple transmembrane domains.

• Most animal cells maintain low internal $Na^+$ and high internal $K^+$.

• Phosphate groups in phospholipids are polar and hydrophilic.