7.1 Lipid bilayers and membrane models

Lipid bilayers form the foundation of cell membranes, creating a barrier between the cell and its environment. These structures consist of two layers of lipid molecules, with proteins embedded within them, allowing for selective permeability and essential cellular functions.

Understanding membrane models is crucial for grasping how cells interact with their surroundings. The fluid mosaic model describes membranes as dynamic structures, while lipid rafts highlight the importance of specialized membrane domains in cellular processes.

Biological Membrane Structure

Lipid Bilayer Composition

• Biological membranes are composed of a lipid bilayer, which consists of two layers of amphipathic lipid molecules with their hydrophobic tails facing inward and their hydrophilic heads facing outward
• The main lipid components of biological membranes are phospholipids, glycolipids, and cholesterol
  • Phospholipids are the most abundant lipids in membranes and include phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol
  • Glycolipids contain a carbohydrate moiety attached to the lipid head group and are found primarily in the outer leaflet of the plasma membrane
  • Cholesterol is a sterol that modulates membrane fluidity and permeability

Protein Integration and Membrane Diversity

• Proteins are embedded within the lipid bilayer and can be classified as integral (transmembrane) or peripheral (associated with the membrane surface)
• Integral proteins span the entire lipid bilayer and often function as channels, receptors, or enzymes (ion channels, G protein-coupled receptors)
• Peripheral proteins are loosely attached to the membrane surface and can dissociate from the membrane under certain conditions (cytoskeletal proteins, enzymes)
• The lipid composition of membranes varies depending on the cell type and organelle, which influences membrane properties and functions
• Different organelles have unique lipid compositions tailored to their specific roles (mitochondrial membranes rich in cardiolipin, endoplasmic reticulum membranes high in phosphatidylcholine)

Fluid Mosaic Model

Dynamic Nature of Membranes

• The fluid mosaic model, proposed by Singer and Nicolson, describes the structure of biological membranes as a fluid, dynamic system with a mosaic of lipids and proteins
• The model emphasizes the lateral mobility of lipids and proteins within the plane of the membrane, allowing for diffusion and reorganization of membrane components
• Lipid molecules can diffuse laterally within their respective leaflets, while proteins can move within the lipid bilayer or along the membrane surface (lateral diffusion)
• The fluidity of the membrane is influenced by factors such as temperature, lipid composition (e.g., the presence of unsaturated fatty acids and cholesterol), and protein-lipid interactions
• Higher temperatures and a greater proportion of unsaturated fatty acids increase membrane fluidity, while cholesterol modulates fluidity by interacting with neighboring lipids

Functional Implications of Membrane Fluidity

• Membrane fluidity is essential for various cellular processes, including signal transduction, membrane trafficking, and cell division
• The fluid nature of membranes allows for the formation of transient or stable membrane domains, such as lipid rafts, which can compartmentalize specific membrane components and functions
• Membrane fluidity enables the rapid diffusion of lipids and proteins, facilitating their interactions and the assembly of functional complexes (receptor-ligand binding, enzyme-substrate interactions)
• Changes in membrane fluidity can affect the function of membrane proteins, such as ion channels and receptors, by altering their conformation or accessibility to ligands

Lipid Rafts in Membranes

Characteristics and Composition of Lipid Rafts

• Lipid rafts are small, dynamic, and ordered domains within the plasma membrane that are enriched in cholesterol, sphingolipids, and specific proteins
• These domains are more tightly packed than the surrounding lipid bilayer due to the high content of saturated fatty acids and cholesterol, resulting in a liquid-ordered state
• Lipid rafts are resistant to solubilization by non-ionic detergents at low temperatures, allowing for their isolation and characterization (detergent-resistant membranes)
• The size of lipid rafts ranges from a few nanometers to several hundred nanometers in diameter, and they can coalesce to form larger platforms

Functional Roles of Lipid Rafts

• Lipid rafts serve as platforms for the assembly and regulation of signaling complexes, such as those involved in T cell activation, B cell signaling, and G protein-coupled receptor signaling
• Proteins can be selectively included or excluded from lipid rafts based on their affinity for the lipid environment, which can modulate their function and interactions
• Lipid rafts are involved in various cellular processes, including membrane trafficking, cell adhesion, and pathogen entry
• Certain pathogens, such as influenza virus and HIV, exploit lipid rafts for entry and budding from host cells
• The dynamic nature of lipid rafts allows for the rapid reorganization of membrane components in response to cellular stimuli or environmental changes
• Disruption of lipid rafts can impair signaling pathways and cellular functions, highlighting their importance in membrane organization and cell physiology

Studying Membrane Structure

Microscopy Techniques

• Electron microscopy techniques, such as transmission electron microscopy (TEM) and scanning electron microscopy (SEM), provide high-resolution images of membrane structure and organization
  • Freeze-fracture electron microscopy allows for the visualization of the distribution of integral membrane proteins by splitting the lipid bilayer and creating replicas of the exposed surfaces
• Fluorescence microscopy, including confocal and super-resolution microscopy, enables the study of membrane dynamics and the localization of specific membrane components using fluorescent probes or tagged proteins
• Fluorescent lipid analogs and membrane dyes can be used to label and visualize lipid domains, such as lipid rafts, in living cells (Laurdan, DiI)

Biochemical and Biophysical Methods

• Lipid extraction and analysis methods, such as thin-layer chromatography (TLC) and mass spectrometry (MS), are used to determine the lipid composition of membranes
• Membrane protein isolation techniques, such as detergent solubilization and affinity chromatography, allow for the purification and characterization of specific membrane proteins
• Spectroscopic methods, such as fluorescence spectroscopy and electron spin resonance (ESR), provide insights into the biophysical properties of membranes and the behavior of membrane components
• Fluorescence recovery after photobleaching (FRAP) and single-particle tracking (SPT) techniques are used to measure the lateral mobility of lipids and proteins within membranes
• Model membrane systems, such as liposomes and supported lipid bilayers, are used to study membrane properties and protein-lipid interactions in a controlled environment
• Liposomes can be prepared with specific lipid compositions to mimic different membrane environments and investigate the effects on protein function and stability