Chapter Five: Part Two

Chapter 5: Membrane Structure and Transport

Overview of Chapter 5

• Topics Covered:

  • Membrane Structure

  • Fluidity of Membranes

  • Overview of Membrane Transport

  • Transport Proteins

  • Exocytosis and Endocytosis

Biological Membranes

• Definition: Biological membranes, primarily made of a phospholipid bilayer.

• Functions:

  • Separate the cell from its environment.

  • Separate the cell into subcellular domains allowing different biochemical processes to occur.

• Components:

  • Phospholipids:

  • Characteristics: Amphipathic with a polar head group that faces outward and two hydrophobic tails that face inward.

  • Cholesterol:

  • Structure is characterized by a four-ring structure.

  • Additional Components:

  • Proteins and carbohydrates, varying in relative amounts.

Important Functions of Cellular Membranes

• Selective uptake and export of ions and molecules.

• Cell compartmentalization.

• Protein sorting.

• Anchoring of the cytoskeleton.

• Production of energy intermediates (ATP and NADPH).

• Cell signaling.

• Cell and nuclear division.

• Adhesion of cells to one another and to the extracellular matrix.

Membranes as Barriers

• Selective Permeability:

  • Membranes exhibit selective permeability to different types of molecules, influencing transport efficiency.

• Permeability Rankings:

  • High Permeability:

  • Gases (e.g., $CO<em>2$, $N</em>2$, $O_2$)

  • Very small uncharged polar molecules (e.g., Ethanol)

  • Moderate Permeability:

  • Water ($H_2O$)

  • Urea ($H<em>2NCONH</em>2$)

  • Low Permeability:

  • Polar organic molecules (e.g., Glucose)

  • Charged ions (e.g., $Na^+$, $K^+$, $Mg^{2+}$, $Ca^{2+}$, $Cl^-$)

  • Very low permeability for large molecules (Proteins, Polysaccharides, Nucleic acids like DNA and RNA).

Phospholipid Membranes

• Structure:

  • Comprised of two hydrophobic tails; hydrophobic due to their non-polar nature, which prevents hydrogen bonding with water.

  • The two leaflets (halves of a bilayer) exhibit asymmetrical properties.

Fluid-Mosaic Model

• Description:

  • A biological membrane is visually a mosaic comprised of lipid, protein, and carbohydrate molecules.

  • Exhibits fluidity, allowing lateral movement of polymers (lipids and proteins).

  • Metaphor: “Protein icebergs adrift on a lipid sea.”

Proteins in Membranes

• Types of Membrane Proteins:

  • Integral or Intrinsic Membrane Proteins:

  • Transmembrane Proteins: Have regions embedded within the hydrophobic part of the bilayer.

  • Lipid-anchored Proteins: Covalently bonded to a phospholipid.

  • Peripheral or Extrinsic Membrane Proteins: Noncovalently bound to integral membrane proteins or polar head groups of phospholipids.

Genomes & Proteomes

• Statistics on Membrane Proteins:

  • Approximately 25% of all genes encode membrane proteins.

  • Predicted that 20–30% of all genes across all domains—archaea, bacteria, eukaryotes—code for membrane proteins.

  • Functions of many of these membrane proteins remain unknown.

Organismal Data on Membrane Proteins:

Membrane Fluidity

• Definition:

  • Membranes are considered semifluid; individual molecules are in close association but can move within the membrane.

• Asymmetry of Leaflets:

  • Most phospholipids can rotate and laterally move, but “flip-flop” movement between leaflets does not occur spontaneously, necessitating flippase that requires ATP.

Factors Affecting Membrane Fluidity

• Length of Fatty Acyl Tails:

  • Shorter tails lead to decreased interaction, increasing fluidity.

• Presence of Double Bonds:

  • Double bonds create kinks in the acyl tails, making the membrane more fluid.

• Presence of Cholesterol:

  • Cholesterol stabilizes membranes but its effects vary with temperature.

Experiments on Lateral Transport

• Research by Larry Frye and Michael Edidin (1970):

  • Demonstrated the lateral movement of membrane proteins through fusion of mouse and human cells under different temperature conditions (0°C vs. 37°C).

• Findings:

  • At 0°C, the mouse membrane protein labeled by fluorescence remained on one side; at 37°C, the protein redistributed across the entire fused cell surface.

Restrictions on Membrane Protein Movement

• Overview:

  • Between 10-70% of membrane proteins may have restricted lateral movement.

  • Integral proteins may associate with cytoskeletal components, limiting mobility.

  • Some proteins associate with extracellular matrix proteins or other cells externally.

Membrane Modifications

• Modification by Carbohydrates:

  • Carbohydrates added to proteins or lipids can modify membrane functionality.

  • Glycosylation: Covalent bonding of carbohydrates to proteins or lipids (e.g., glycolipids for lipids, glycoproteins for proteins).

  • Carbohydrates are mostly attached on the extracellular side.

Glycosylation Mechanisms

• Types:

  • N-linked: Attachment of carbohydrates to the nitrogen atom of asparagine side chains.

  • O-linked: Occurs exclusively in the Golgi apparatus, involving the addition of sugars to oxygen atoms of serine or threonine side chains.

• Process:

  1. A group of 14 sugars is built onto a lipid in the endoplasmic reticulum membrane.

  2. Oligosaccharide transferase transfers the carbohydrate tree to an asparagine in the polypeptide.

  3. Completes the synthesis of the polypeptide.

Functions of Glycoproteins and Glycolipids

• Cell-Cell Functions:

  • Involved in cell-cell adhesion and migration during development.

  • Critical for cell-cell recognition (e.g., immune system functions).

  • Facilitate cell-substrate recognition (e.g., mannose-6-P targets proteins to lysosomes).

• Protection:

  • Contribute to the glycocalyx, which protects cells.

The Glycocalyx

• Overview:

  • Comprises the carbohydrate-rich zone on the cell surface important for various functions including protection, adhesion, and signaling.