The Structure and Function of the Cell Membrane

Course Structure: Membrane and Transport Lectures

The lecture series is organized into five primary sessions focusing on the mechanics of cellular transport:

1. Lecture 1: The structure and function of the cell membrane.

2. Lecture 2: Transport across cell membranes.

3. Lecture 3: Transport across cells: Epithelial transport of glucose.

4. Lecture 4: Transport across cells: Chloride secretion and cystic fibrosis.

5. Lecture 5: Laboratory and lecture review.

Rules of Engagement and Communication

• Canvas/Piazza: Students are instructed to use the CANVAS platform to raise questions in the Piazza forum.

• Review Lecture: Areas of concern identified by students during the course will be addressed in detail during the scheduled review lecture.

The Fluid Mosaic Model of Membrane Structure

General Characteristics

• Dimensions: The membrane is a thin, flexible, and sturdy barrier measuring approximately $8\,nm$ ($8 \times 10^{-9}\,m$) in thickness.

• Proportions: The membrane consists of approximately $50\%$ lipid and $50\%$ protein by mass.

• The Model: Described as a "sea of lipids in which proteins float like icebergs."

• Stability: The structure is held together primarily by hydrogen bonds.

Composition of the Lipid Bilayer

The membrane is formed by two back-to-back layers comprising three types of lipid molecules:

1. Phospholipids ($75\%$): The primary structural component.

2. Cholesterol: Scattered throughout the double row of phospholipids.

3. Glycolipids: Scattered among the lipids, often involved in cell signaling.

Phospholipid Biochemistry

Phospholipids are amphipathic, meaning they possess both polar and non-polar regions:

• Polar Heads: These are charged and hydrophilic (water-loving). They form the surfaces that interact with the aqueous extracellular fluid and the cytoplasm.

• Non-polar Tails: These consist of fatty acid chains that are hydrophobic (water-fearing) and face each other to form the hydrophobic core of the membrane.

Membrane Fluidity

Membranes are dynamic, fluid structures where lipids are capable of lateral movement within the plane of the membrane leaflet. However, lipids rarely "flip-flop" (transverse movement) from one leaflet to the other, which allows for the maintenance of asymmetric lipid composition between the inner and outer leaflets.

Factors Determining Fluidity

• Lipid Tail Length: Longer tails increase van der Waals interactions, making the membrane less fluid.

• Number of Double Bonds: A higher number of double bonds (unsaturation) in the fatty acid tails increases fluidity by creating kinks that prevent tight packing.

• Cholesterol Content: At physiological temperatures, an increase in cholesterol concentration decreases membrane fluidity by stabilizing the structure.

Varieties of Membrane Proteins

Membrane proteins are categorized based on their relationship with the lipid bilayer:

1. Integral Proteins: These are amphipathic proteins that extend into or completely across the cell membrane (transmembrane proteins). Their hydrophobic regions consist of non-polar amino acids usually coiled into helices to interact with the lipid core, while their hydrophilic ends interact with aqueous solutions.

2. Peripheral Proteins: These are attached to the inner or outer surface of the membrane rather than being embedded. They are weakly bound and can be easily removed.

Functional Classifications of Proteins

• Ion Channels: Form pores for specific ions to cross the membrane.

• Transporter Proteins: Move substances across the membrane by changing shape.

• Receptor Proteins: Bind to specific ligands to trigger cellular responses.

• Enzymes: Catalyze specific chemical reactions at the membrane surface.

• Linkers: Anchor the membrane to the cytoskeleton or adjacent cells.

• Cell Identity Markers: Allow cells to recognize one another (e.g., glycoproteins).

Selective Permeability

The lipid bilayer acts as a selective barrier, allowing only specific molecules to pass through the hydrophobic core without assistance.

• Highly Permeable to:

  • Non-polar, uncharged molecules: $O_2$, $N_2$, benzene.

  • Lipid-soluble molecules: Steroids, fatty acids, and some vitamins.

  • Small, uncharged polar molecules: $H_2O$, urea, glycerol, and $CO_2$.

• Impermeable to:

  • Large, uncharged polar molecules: Glucose and amino acids.

  • Ions: $Na^+$, $K^+$, $Cl^-$, $Ca^{2+}$, and $H^+$ (protons).

Membrane proteins act as "gatekeepers" to mediate the transport of these impermeable substances.

Principles of Diffusion

Diffusion is defined as the random mixing of particles in a solution due to the particles' kinetic energy. Net diffusion occurs from a region of higher concentration to a region of lower concentration until equilibrium is reached.

Kinetic Factors Influencing Diffusion Rate

• Concentration Gradient: A greater difference in concentration between two sides of a membrane results in a faster rate of diffusion.

• Temperature: Higher temperatures increase kinetic energy, speeding up the rate of diffusion.

• Molecular Size: Larger substances diffuse more slowly.

• Surface Area: An increase in membrane surface area increases the rate of diffusion.

• Diffusion Distance: Increasing the distance a substance must travel (e.g., a thicker membrane) slows the rate of diffusion.

Physical and Biological Consequences

• Size Limit: The slow rate of diffusion over long distances sets a limit on the maximum size of cells to approximately $20\,\mu m$.

• Efficiency: Diffusion is extremely efficient over very small distances.

• Cellular Adaptation: To increase transport, cells can increase surface area (e.g., microvilli).

Electrochemical Gradients and Energy Storage

Types of Gradients

1. Concentration Gradient: The difference in chemical concentration between the inside and outside of the cell. Uncharged molecules diffuse down this gradient.

2. Electrical Gradient: The difference in electrical charge across the membrane (membrane potential). Ions are influenced by this potential.

3. Electrochemical Gradient: The combined influence of concentration and electrical gradients on the movement of ions.

The Plasma Membrane as a Capacitor

Membranes mimic capacitors in physics; they are able to separate and store electrical charge. Cells maintain a negative charge relative to the extracellular fluid.

Typical Ion Distributions

• Extracellular Fluid: High concentrations of $Na^+$ and $Cl^-$, and low concentrations of $K^+$.

• Cytoplasm: High concentrations of $K^+$, and low concentrations of $Na^+$ and $Cl^-$.

• Energy Consumption: Cells expend approximately $30\%$ of their resting energy to maintain these concentration and electrical gradients. These gradients represent significant stored energy.

Osmosis and Osmotic Pressure

Osmosis is the net movement of water ($H_2O$) across a selectively permeable membrane from an area of higher water concentration (dilute solution/low solute) to an area of lower water concentration (concentrated solution/high solute).

• Requirements: Osmosis only occurs if the membrane is permeable to water but impermeable to specific solutes.

• Osmotic Pressure: This is defined as the amount of pressure that must be applied to a solution to prevent the inward flow of water across a semi-permeable membrane. Differences in osmolarity drive the movement of water across biological membranes.