Lecture 3-1: The Lipid Bilayer

Function of Lipid Bilayers

• Separation of Spaces

  • Lipid bilayers act as barriers that separate intracellular spaces from the external environment.

  • Cells maintain isolated spaces capable of regulated exchanges with their surroundings.

  • An ideal barrier is impermeable to most molecules in both the environment and the cell.

  • Biological molecules are primarily hydrophilic; a purely hydrophobic barrier would destabilize in aqueous environments.

Characteristics of the Plasma Membrane

• Multi-functional Structure

  • The plasma membrane is dynamic and not rigid.

  • Functions of the plasma membrane include:

    • Evaluating and communicating with the environment.

    • Acquiring necessary molecules while discarding waste.

    • Facilitating traversal through the environment.

Internal Membranes in Eukaryotic Cells

• Compartmentalization

  • Organelles in eukaryotic cells are separated by their own internal membranes, allowing distinct reactions in isolated regions.

  • Functions of specific organelles:

    • Endoplasmic Reticulum (ER): Lipid sorting, membrane-bound and secreted protein synthesis.

    • Peroxisome: Oxidation of long fatty acids.

    • Lysosome: Hydrolysis of unneeded macromolecules.

    • Golgi Apparatus: Protein modification and trafficking.

    • Mitochondrion: RedOx reactions for energy extraction.

Composition of Cell Membranes

• Lipid Bilayers and Proteins

  • Cell membranes consist mainly of a bilayer of phospholipids and associated proteins.

  • Certain proteins and lipids create distinct functional regions called "rafts" within the plasma membrane.

Phospholipids as Key Components

• Structure of Phospholipids

  • Phospholipids have a polar (hydrophilic) head and nonpolar (hydrophobic) tails.

  • Overall structure includes:

    • Choline group

    • Phosphate group

    • Glycerol backbone

    • Two hydrocarbon tails

Hydrophilic Molecules Interaction

• Hydrogen Bonding

  • Hydrophilic molecules form hydrogen bonds with water.

  • Example: Acetone interacting with water showing δ+ and δ- charges.

Hydrophobic Molecules Interaction

• Exclusion from Hydrogen Bonds

  • Hydrophobic molecules, like triacylglycerol and 2-methylpropane, do not form extensive interactions with water and are excluded from hydrogen bond networks.

Amphipathic Nature of Membrane Lipids

• Different Membrane Lipids

  • Various lipids (e.g., phosphatidylserine, cholesterol, and galactocerebroside) demonstrate amphipathic properties, having both hydrophilic heads and hydrophobic tails.

Amphipathic Lipid Behavior in Water

• Bilayer Formation

  • In water, amphipathic lipids arrange into bilayers to maximize polar interactions and minimize hydrophobic contact with water.

  • The hydrophobic region is thicker; charged and polar molecules struggle to cross lipid bilayers.

Stability through Sphere Formation

• Lipid Bilayer Stability

  • Lipid bilayers can be unstable in water due to exposure of hydrophobic layers.

  • Formation of bilayer spheres prevents exposure to water and is energetically favorable, leading to spontaneous liposome formation.

Lipid Dynamics within the Bilayer

• Dynamic Lipid Movement

  • Lipid movements include:

    • Lateral diffusion: Movement within the same leaflet.

    • Flexion: Tails repositioning relative to head groups.

    • Rotation: Spinning of lipids.

    • Flip-flop: Moving from one leaflet to another (energetically unfavorable).

  • Flip-flop movement is facilitated by enzymes called flippases.

Influence of Membrane Composition on Fluidity

• Fluidity Factors

  • Membrane fluidity reflects lipid movement freedom; higher fluidity = softer membrane.

  • Temperature and lipid saturation affect fluidity. Unsaturated lipids increase membrane fluidity, while saturated lipids decrease it.

  • Cholesterol acts as a fluidity buffer, stabilizing membrane fluidity at different temperatures.

Membrane Assembly in the ER

• Membrane Formation Origins

  • Membranes originate from the endoplasmic reticulum (ER) with phospholipid synthesis starting in the cytosol.

  • Enzymatic modifications and random distribution of lipids occur, leading to symmetrical leaflets.

  • Membrane asymmetry is established later in the cell.

Establishing Asymmetry in the Golgi

• Role of the Golgi

  • The Golgi apparatus modifies lipid membranes to create asymmetry using flippases, which consume ATP for lipid movement across leaflets.

  • This asymmetrical distribution contributes to the functioning of various cellular membranes.

Membrane Orientation Consistency

• Maintaining Orientation

  • Established membrane face compositions and orientations of transmembrane proteins are preserved during transport.

  • Secreted proteins are retained within organelles until release, stored efficiently for quick response.

Functional Significance of Asymmetrical Lipid Distribution

• Glycolipid and Membrane Function

  • Glycolipids are located in the extracellular leaflet, forming the glycocalyx and serving as recognition sites for cells.

  • Phosphatidylinositol is key in intracellular signal transduction and is localized to the cytosolic leaflet.

Health Indicators via Lipid Distribution

• Phosphatidylserine Flipping and Cell Health

  • Phosphatidylserine normally resides in the cytosolic leaflet; flipping to the extracellular leaflet indicates apoptosis, acting as a signal for phagocytic cells.

  • Techniques like flow cytometry utilize labeled annexin V to detect apoptotic cells.

Key Concepts Summary

• Membrane Basics

  • Membranes segregate cellular spaces and facilitate organelle reactions in eukaryotes.

  • Amphipathic lipids naturally form bilayers in water, minimizing hydrophobic exposure.

  • Membrane assembly starts in the ER, with subsequent modifications in the Golgi that enhance asymmetry.

  • Fluidity is linked to lipid movement; flippases assist in maintaining asymmetry essential for cellular function.

Here are some mnemonics to help remember key concepts related to lipid bilayers and cell membranes.

1. Functions of the Plasma Membrane: Evaluate, Acquire, Discard, Facilitate - EADFF ("Every Amazing Dolphin Flies") - Remember that the plasma membrane evaluates and communicates with the environment, acquires necessary molecules, discards waste, and facilitates traversal.

2. Components of Phospholipids: Choline, Phosphate, Glycerol, Tails - CPGT ("Can Penguins Glide Together?") - Recall the structure includes a choline group, phosphate group, glycerol backbone, and two hydrocarbon tails.

3. Dynamic Lipid Movement: Lateral diffusion, Flexion, Rotation, Flip-flop - LFRF ("Little Frogs Run Fast") - Helps remember the different types of lipid movements within the bilayer.

4. Fluidity Factors: Temperature, Unsaturated lipids, Saturated lipids, Cholesterol - TUSC ("Tigers Understand Sweet Corn") - To remember how temperature and lipid saturation affect fluidity and the role of cholesterol as a buffer.

5. Membrane Origin: Endoplasmic reticulum, Phospholipid synthesis, Modifications - EPM ("Every Patient Matters") - To remember the origin of membranes and their synthesis in the ER and subsequent modifications.