Lecture #7 – Biomembrane Structure

Exam Information

  • Exam #1 is scheduled for TONIGHT!

  • Date: Thursday, September 11th

  • Time: 5:00 to 6:20 pm

  • Location: Lloyd Hall, Rm 16!!!

Lecture #7 – Biomembrane Structure

  • Major Topics Covered (from Chapter 10, pages 442-469):

    • 10.1 The Lipid Bilayer: Composition and Structural Organization

    • 10.2 Membrane Proteins: Structure and Basic Functions

    • 10.3 Phospholipids, Sphingolipids, and Cholesterol: Synthesis and Intracellular Movement

Learning Objectives

  • Describe the functions of cellular membranes.

  • Elucidate the chemical components and properties of cell membranes.

  • Describe the development of the models to the Fluid-Mosaic Model.

  • Explain the role of carbohydrates in membrane structure.

  • Describe the types of proteins found in membranes and their roles.

  • Stress the importance and detection of membrane fluidity in living cells.

  • Describe biological membrane asymmetry.

Important Concepts about the Lipid Bilayer: Composition and Structural Organization

  • Membranes are barriers between aqueous compartments.

  • Amphipathic phospholipids spontaneously form bilayers with:

    • Hydrophilic faces

    • Hydrophobic core

  • Biological membranes:

    • Vary in lipid composition.

    • Are impermeable to water-soluble molecules and ions.

    • Have a viscous consistency with fluidlike properties.

The Plasma Membrane

  • Definition: The plasma membrane is the outer boundary of the cell separating it from the environment.

  • Features:

    • It is a thin, fragile structure about 5 – 10 nm thick.

    • Not detectable with a light microscope; requires an electron microscope.

    • Dark-staining layers seen in electron micrographs are mainly the inner and outer polar surfaces of the bilayer.

    • All closely examined membranes (plasma, nuclear, or cytoplasmic) from various organisms have the same ultrastructure.

Overview of Membrane Functions

  • Compartmentalization: Membranes form continuous sheets that enclose intracellular compartments.

  • Scaffold for biochemical activities: Membranes provide a framework that organizes enzymes for effective interactions.

  • Selectively permeable barrier: Membranes allow regulated exchange of substances between compartments.

  • Transporting solutes: Membrane proteins facilitate the movement of substances between compartments.

  • Responding to external signals: Membrane receptors transduce signals from outside the cell in response to specific ligands.

  • Intracellular interaction: Membranes mediate recognition and interaction between adjacent cells.

  • Energy transduction: Membranes transduce photosynthetic energy, convert chemical energy to ATP, and store energy.

Plasma Membrane Structure

  • Fluid Mosaic Model: Describes the plasma membrane's architecture as a phospholipid bilayer (~3 nm wide) with embedded proteins.

  • Fluidity: Membranes exhibit fluid-like properties similar to that of olive oil; noncovalent interactions maintain integrity and resilience.

  • Movement: Individual phospholipids spin and diffuse laterally within the plane of the membrane.

Eukaryotic Cellular Membranes

  • Dynamic structures:

    • Membrane fluidity and flexibility allow organelles to assume typical shapes.

    • Enable membrane budding and fusion, illustrated by the Golgi complex's stacked membranes involving budding vesicles for intracellular trafficking.

The Bilayer Structure of Biomembranes

  1. Composition: Composed of amphipathic phosphoglycerides, sphingolipids, and cholesterol.

  2. Influence on structure: A diverse group of lipids influences membrane structure and protein activity.

  3. Energetically favorable bilayer formation:

    • Spontaneous formation occurs through hydrophobic interactions.

    • Stabilizing forces include van der Waals interactions between hydrocarbon tails.

    • Polar head groups interact through ionic and hydrogen bonds with each other and with hydrophilic molecules (e.g., H2O, proteins).

Membrane Phospholipids

  • Amphipathic molecules:

    • Hydrophobic fatty acid-based tails (water-fearing).

    • Hydrophilic polar head groups (water-loving).

Formation of the Lipid Bilayer

  • Micelles: At high concentrations of fatty acids in water, they form micelles, which consist of a hydrophobic interior made entirely of fatty acyl chains.

  • Bilayers: At high concentrations of phospholipids in water, they form bilayers (liposomes) that encase an aqueous compartment; they spontaneously aggregate to form bilayers.

  • SDS (Sodium dodecyl sulfate): Used in studies of lipid structures.

Lipids in Membrane Architecture

  • Triglycerides: Cannot spontaneously form lipid bilayers due to the glycerol backbone's weak amphipathic nature.

  • Phosphoglycerides: They carry a charged phosphate and can possess fully charged polar head groups, making them very amphipathic and providing stability via hydrophobic group burial out of contact with water.

The Faces of Cellular Membranes

  • Plasma Membrane: A single bilayer that encloses the cell, having cytosolic and exoplasmic leaflets.

  • Vesicles and organelles: Bounded by single membranes with an internal aqueous space that is topologically equivalent to the extracellular medium.

  • Nucleus, mitochondria, chloroplast: Enclosed by double membranes with an intermembrane space.

Membrane Budding and Fusion

  • Endocytosis: Plasma membrane segment buds inward toward the cytosol and pinches off a separate vesicle. Cytosolic face remains facing the cytosol; exoplasmic face faces vesicle lumen.

  • Exocytosis: An intracellular vesicle fuses with the plasma membrane, connecting the vesicle lumen with the extracellular medium while the cytoplasmic face remains facing the cytoplasm.

  • Asymmetric orientation: Membrane-spanning proteins retain their orientation during vesicle budding and fusion; their segments always face the cytosol.

The Chemical Composition of Membranes

  • Membrane components:

    • Lipid and protein components are bound together by non-covalent bonds.

    • Membranes contain carbohydrates that vary in protein/lipid ratios among different membrane types.

  • Types of membrane lipids:

    • Phosphoglycerides: Diacylglycerides with small functional head groups linked by phosphate ester bonds (all phospholipids).

    • Sphingolipids: Ceramides formed by sphingosine attachment to fatty acids (some are phospholipids).

    • Sterols: Smaller, less amphipathic lipids found in animals (cholesterol), fungi (ergosterol), and plants (stigmasterol).

Phosphoglycerides

  • Structure:

    • Glycerol backbone with two esterified hydrophobic fatty acyl chains that vary in length (commonly 16-18 carbons) and saturation (either saturated or unsaturated).

    • Polar group esterified to the phosphate serves as the head.

Classification of Phosphoglycerides

  • Major head groups:

    • Phosphatidylcholine (PC)

    • Phosphatidylethanolamine (PE)

    • Phosphatidylserine (PS)

    • Phosphatidylinositol (PI)

  • Plasmalogens: One fatty acyl chain attached to glycerol by an ester linkage and one by an ether linkage, sharing the same head groups as other phosphoglycerides.

Sphingolipids

  • Derivatives of sphingosine: Formed by attaching various fatty acyl chains by an amide bond.

  • Sphingomyelins (SM): Contain a phosphocholine head group (phospholipid).

  • Glycolipids: Include a sugar residue or a branched oligosaccharide attached to the sphingosine backbone (e.g., glucosylcerebroside with a glucose head group).

Sterols

  • Types:

    • Cholesterol in animals, ergosterol in fungi, and stigmasterol in plants.

  • Prevalence: Can comprise up to 50% of animal membrane lipids.

  • Amphipathic structure:

    • Head group: single polar hydroxyl group.

    • Tail: conjugated four-ring hydrocarbon plus a short hydrocarbon chain.

Membrane Lipids and Fluidity

  • State of membrane lipids: Exists in gel or fluid consistency depending on temperature, lipid composition, and saturation, influenced in presence of cholesterol.

  • Transition temperature: The temperature at which lipids change from liquid to gel, dependent on length and degree of saturation.

  • Fluid state: Phospholipids with short fatty acyl chains form fewer van der Waals interactions and cis-unsaturation puts kinks in the chains.

Importance of Membrane Fluidity

  • Compromise: Between rigidity and fluidity allows for movement and assembly within the membrane.

  • Exchange rate: Phospholipids can exchange places with neighbors ~10^7 times/sec, and lateral diffusion is several micrometers per second, indicating bilayers are ~100 times more viscous than water, comparable to olive oil.

  • Flip-flop movement: From leaflet to leaflet occurs rarely due to a high energetic barrier.

Maintaining Membrane Fluidity

  • Adaptation: Organisms (non-birds and mammals) adjust fluidity in response to temperature changes through lipid composition alterations.

  • Lipid bilayer remodeling: Involves saturation or desaturation of acyl chains and phospholipases or acyltransferases replacing acyl chains.

  • Cholesterol's role: Prevents regular packing of saturated fatty acyl chains, abolishes sharp transition temperatures, and enhances rigidity while preserving fluidity.

Regulation of Membrane Fluidity

  • Importance: Maintaining membrane fluidity is crucial for cellular structure; research indicates cells can adjust fluidity in specific membrane regions, referred to as lipid rafts.

  • Homeoviscous adaptation: Observed in poikilothermic organisms with temperature-dependent adjustments in saturated fatty acids.

Major Lipid Components of Selected Biomembranes

  • Lipid composition: Characteristic of specific membranes, essential for membrane fusion, networking, and charge separation.

  • Membrane synthesis: Reflects lipid distribution asymmetry and synthesis locations in the endoplasmic reticulum and Golgi.

The Asymmetry of Membrane Lipids

  • Functional implications: Inner and outer membrane leaflets have different lipid compositions providing distinct physicochemical properties suitable for varied interactions; movement within a leaflet is common, while “flip-flopping” occurs rarely.

Effect of Lipid Composition

  • Influence on bilayer thickness: Membrane protein distribution varies with bilayer thickness; pure sphingomyelin bilayers are thicker than phosphoglyceride bilayers, while cholesterol increases thickness of phosphoglyceride bilayers (lipid rafts are also thicker).

Lipid Rafts

  • Specialized regions: The outer leaflet's plasma membrane contains regions where cholesterol and sphingolipids aggregate to form ordered microdomains that float within a more fluid environment, allowing for favorable interactions for receptors and GPI-anchored proteins.

Effect of Lipid Composition on Curvature

  • Shapes of phospholipids:

    • PC has a cylindrical shape, whereas PE has a conical shape; the interaction results in natural curvature of membranes enriched with specific lipids.

Membrane Proteins: Structure and Functions

  • Types of proteins: Integral, lipid-anchored, and peripheral proteins are present in biological membranes.

  • Integral membrane proteins: Comprise 20-30% of all encoded proteins, containing hydrophobic membrane-spanning domains.

  • Membrane proteins' distinct sidedness: They attach asymmetrically to the bilayer.

Membrane Protein Classes

  1. Integral proteins: Penetrate and cross the lipid bilayer, amphipathic with hydrophobic domains anchoring them and hydrophilic regions forming functional domains.

  2. Channel proteins: Contain hydrophilic cores that create aqueous channels.

  3. Peripheral proteins: Attached outside the bilayer via noncovalent bonds and easily solubilized.

Specific Cases of Membrane Proteins

  • Dimeric Glycophorin: Features a single membrane-spanning α-helix with hydrophobic side chains, and charged residues that anchor it in the membrane.

    • The extracellular and cytosolic domains are rich in charged residues, influencing membrane interactions.

Aqueous Channels and Membrane Proteins

  • α-helical structures: Often form aqueous channels, located within the transmembrane proteins formed by hydrophilic residues facing the channel while hydrophobic residues point outward.

Polar Residues and Multimeric Proteins

  • Assembly guidance: Polar or charged residues within α-helical transmembrane segments can orchestrate the assembly and stabilization of multimeric membrane proteins such as the T cell receptor (TCR) through electrostatic attractions.

Membrane Carbohydrates

  • Presence on membrane surfaces: Carbohydrates linked covalently to lipids (glycolipids) and proteins (glycoproteins) assist in interactions outside of the cell and are essential for cell-cell recognition.

Phospholipids, Sphingolipids, and Cholesterol: Synthesis and Movement

  • Membrane growth: Cells synthesize new membranes by expanding existing membranes.

  • Fatty acid characteristics: Composed of saturated/unsaturated fatty acids varying in chain lengths, synthesized in the ER and moved by flippases or other mechanisms.

Transport Mechanisms for Lipids

  • Proposed methods: Lipids like cholesterol and phospholipids are transported through:

    • Vesicular budding: Ion transfer via vesicles from one membrane to another.

    • Direct transfer: Through membrane-embedded proteins between membranes in contact.

    • Lipid-transfer proteins: Small, soluble proteins facilitating transfer between organelles.

Phospholipid Synthesis in the ER

  • Synthesis pathway: Involves several key steps starting from Acetyl CoA leading to the formation of phosphatidylcholine and related compounds through specific cytosolic enzymes and membrane structures to assist in leaflets' formation.

Upcoming Topics

  • Next Lecture: Focus on transmembrane transport of ions and small molecules.

  • Reading Assignment: Chapter 11, pages 470-511.

  • Next quiz: Available on Achieve site until 8:00 am on Tuesday (September 16th).