Lecture 7_ BIOC212_Membranes 1_Maria2025_to PDF

Lecture 7: Membrane Proteins – 1

• Course: BIOC 212

• Instructor: Maria Vera Ugalde

• Term: Winter 2024

Outline of Lecture 7

• Cell Compartments: Organelles of the secretory pathway and membranes

• Biological Membranes: Characteristics and Composition

• Membrane Lipids

• Membrane Assembly

• Membrane Microdomains

• Lipid Synthesis and Transport

• Reference: Molecular Biology of the Cell (7th edition), Chapter 10

Overview of Cellular Structure

• Actin Filaments and Microtubules: Key components of the cytoskeleton

• Organelles:

  • Centrosome with centrioles

  • Chromatin (DNA)

  • Extracellular Matrix

  • Nuclear Components: Nuclear pore, nuclear envelope, nucleolus, nucleus

  • Endoplasmic Reticulum (ER), Mitochondrion, Golgi Apparatus, Lysosome, Peroxisome

• Ribosomes in cytosol

• Plasma Membrane

Secretory Pathway

• Definition: Transport system connecting organelles to the plasma membrane

• Processes Involved:

  • Synthesis: Of proteins and lipids in the ER

  • Traffic: Through the Golgi to the plasma membrane

  • Endosomal Internalization: Leads to degradation in lysosomes

• Note: Some organelles (like mitochondria) are not linked to the secretory pathway

Lumen vs. Cytosol

• Lumen: Interior of secretory organelles is continuous with each other and the extracellular space

• Vesicle Functionality: Vesicles can bud one membrane and fuse with another without leaking into the cytosol

• Comparative Environments:

  • Luminal environments (salts, pH, proteins) are similar to extracellular space but differ significantly from the cytosol

Compartment Contents

• Cytosol:

  • High concentrations of K+

  • Low Na+, almost no Ca2+

  • Contains ATP, GTP, cofactors

  • pH ~7.2

• Lumenal/Extracellular Fluid:

  • High Na+, free Mg2+, and decreasing Ca2+ concentrations

  • Specific pH values: e.g., lysosomes (pH 5.0)

Characteristics of Biological Membranes

• Functions:

  • Enclosure of cells and organelles

  • Regulated transport of materials

  • Sites for biochemical reactions (e.g., photosynthesis, metabolism)

  • Enable cell interactions, motility, and signaling

Membrane Properties

• Formation of Hydrophobic Barriers: Separates aqueous environments

• Flexibility: Can change shape

• Selective Permeability:

  • Allows passage of small hydrophobic molecules

  • Larger or charged/polar molecules require transport systems

  • Energy storage via concentration gradients

Fluid Mosaic Model of Membranes

• Consist of lipid bilayers and embedded proteins

• Bilayer structure: Polar heads outside, hydrophobic cores inside

• Membrane proteins exhibit lateral mobility within the bilayer

Membrane Lipids

• Major Types:

  • Phospholipids: Found in all membranes

  • Glycolipids: Present only at plasma membrane

  • Cholesterol: Modulates fluidity and stability

• Lipid Structure: Composed of polar heads and hydrophobic tails

• Impact on Membrane Properties: Affects mobility, curvature, and thickness

Phospholipid Structure

• Abundance: Most common type of membrane lipid

• Head Groups: Include choline, ethanolamine, serine

• Fatty Acid Tails:

  • Typically 14-24 carbons long

  • Can be saturated or unsaturated affecting flexibility and structure

Glycolipids and Cholesterol

• Glycolipids: Located on the external surface, important for cell interactions

• Cholesterol: Provides rigidity, affects phospholipid mobility and tail flexibility

Membrane Asymmetry

• Biological membranes often have asymmetric lipid compositions

• Plasma Membrane Example:

  • Outer leaflet rich in glycolipids

  • Inner leaflet has a negative charge due to high levels of phospatidylserine (PS)

  • Asymmetry maintained actively

Organelle Lipid Composition

• Varies based on biological roles; e.g., PM has high cholesterol, ER has high phosphatidylcholine (PC) and phosphatidylethanolamine (PE)

Microdomains

• Regions of membranes organized laterally

• Lipid Rafts: Enriched in cholesterol, thicker than surrounding membranes, and specialized protein content

Lipid Synthesis

• Location: Occurs on the cytosolic side of the ER

• Phospholipid synthesis involves multiple steps from fatty acid attachment to glycerol-phosphate formation

• Role of Scramblases: Flip lipids randomly in the ER membrane

Transport Mechanisms

• Lateral Organization: Lipid transport occurs via vesicles, carrier proteins, and organelle contact sites

• Key for maintaining membrane asymmetry and functionality

Comparison of Lipid Types

• Criteria for Comparison: Polarity, charge, size, and hydrophobicity of different lipid classes (e.g., phospholipids, glycolipids, cholesterol)