Membranes: Their Structure, Function, and Chemistry (Chapter 7 Study Notes)

Membranes: Their Structure, Function, and Chemistry

The Functions of Membranes

Biological membranes are essential for compartmentalization and regulation of cellular processes. They serve as dynamic barriers and platforms for various cellular activities.

• Boundary and Permeability Barrier: Membranes define cell boundaries and regulate the passage of substances.

• Organization and Localization of Function: Membranes compartmentalize cellular processes, allowing specialized environments.

• Transport Processes: Membranes mediate the selective transport of ions and molecules (e.g., Na+, K+, nutrients).

• Signal Detection: Membranes contain receptors for signal transduction.

• Cell-to-Cell Interactions: Membranes facilitate communication and adhesion between cells.

The Fluid Mosaic Model

The fluid mosaic model describes the structure of cell membranes as a mosaic of proteins floating in or on a fluid lipid bilayer.

• Lipid Bilayer: The fundamental structure, providing fluidity and flexibility.

• Integral and Peripheral Proteins: Proteins are embedded within or attached to the bilayer, contributing to diverse functions.

• Dynamic Nature: Both lipids and proteins can move laterally within the layer, allowing membrane flexibility.

Protein/Lipid Ratios Differ in Different Membranes

The composition of proteins and lipids varies among different biological membranes, reflecting their specialized functions.

Membrane	Protein (%)	Lipid (%)	Protein/Lipid Ratio
Plasma membrane (human erythrocyte)	49	43	1.14:1
Mammalian liver cell	54	46	1.17:1
Amoeba	44	56	0.79:1
Myelin sheath of nerve axon	18	79	0.23:1
Nuclear envelope	66	32	2.06:1
Endoplasmic reticulum	63	27	2.33:1
Golgi apparatus	65	29	2.24:1
Chloroplast (thylakoid)	70	30	2.33:1
Mitochondrial outer membrane	55	45	1.22:1
Mitochondrial inner membrane	78	22	3.54:1
Gram-positive bacterium	75	25	3.00:1

Table purpose: Comparison of protein and lipid content in various biological membranes.

Major Classes of Membrane Lipids

Membranes contain a diverse array of lipids, each contributing to membrane structure and function.

• Phospholipids: The most abundant membrane lipids, including phosphoglycerides and sphingolipids. Their kinds and proportions vary among membranes.

• Glycolipids: Lipids with carbohydrate groups attached. Two main types: glycerol-based and glycosphingolipids (cerebrosides and gangliosides).

• Sterols: Present in significant amounts in eukaryotic membranes. Main sterol in animals is cholesterol; in plants, phytosterols; in fungi, ergosterol.

Phospholipids

• Composed of a glycerol backbone, two fatty acids, and a phosphate group (often with an additional polar group).

• Phosphoglycerides and sphingolipids are the two main types.

• Provide the basic structure of the lipid bilayer.

Glycolipids

• Formed by the addition of carbohydrates to lipids.

• Types:

  • Glycerol-based

  • Glycosphingolipids (sphingosine-based):

    • Cerebrosides: Neutral head group.

    • Gangliosides: Negatively charged head group.

Sterols

• Essential for membrane fluidity and stability.

• Cholesterol (animals), phytosterols (plants), ergosterol (fungi).

• Target for antifungal medications (e.g., nystatin targets ergosterol).

Membrane Asymmetry

Lipids are distributed unequally between the two monolayers of the bilayer, resulting in membrane asymmetry.

• Outer Layer: Enriched in glycolipids.

• Inner Layer: Enriched in phosphatidylinositol (PI) and phosphatidylserine (PS).

• Asymmetry is established during membrane synthesis and is maintained over time.

• Transverse diffusion (flip-flop) is rare; lateral diffusion is common.

The Lipid Bilayer is Fluid

Membrane fluidity is crucial for proper function and is influenced by lipid composition and temperature.

• FRAP (Fluorescence Recovery After Photobleaching): Technique to measure lipid mobility in membranes.

• Membranes must remain fluid for optimal function; fluidity decreases below the transition temperature ($T_m$).

• $T_m$ (transition temperature) is the temperature at which the membrane transitions from a fluid to a gel-like state.

Effects of Fatty Acid Composition on Membrane Fluidity

• Chain Length: Increasing fatty acid (FA) chain length increases $T_m$ and decreases fluidity.

• Saturation: Increasing FA saturation increases $T_m$ and decreases fluidity.

Effects of Sterols on Membrane Fluidity

• Cholesterol acts as a fluidity buffer: Decreases fluidity and increases $T_m$ at high temperatures, but prevents tight packing at low temperatures, thus maintaining fluidity.

Lipid Rafts

Lipid rafts are specialized microdomains within membranes, enriched in cholesterol and glycosphingolipids, and play key roles in cell signaling.

• 1-2 nm thicker and less fluid than the surrounding membrane.

• Protein-enriched, especially in GPI-anchored proteins.

• Important for organizing signaling molecules.

Membrane Proteins: Structure and Types

Membranes contain a mosaic of proteins, each with specific structural and functional roles.

Integral Membrane Proteins

• Embedded within the lipid bilayer.

• Types:

  • Integral monotopic proteins: Associated with only one side of the membrane.

  • Transmembrane proteins: Span the bilayer with one or more α-helical or β-barrel segments; can be singlepass or multipass; may form multi-subunit complexes.

Peripheral Membrane Proteins

• Bind to membrane surfaces via weak electrostatic forces and hydrogen bonds.

• Can be removed by changes in pH or ionic strength.

Lipid-Anchored Membrane Proteins

• Covalently attached to lipid molecules within the membrane.

• Types:

  • Fatty acid-anchored: Attached to saturated fatty acids.

  • Isoprenylated: Modified by addition of isoprenyl groups (5C units).

  • GPI-anchored: Linked to glycosylphosphatidylinositol (GPI), synthesized in the ER.

Functions of Membrane Proteins

• Enzymes: Catalyze specific reactions at the membrane surface.

• Solute Transport: Facilitate movement of molecules via channels, transporters, and ATPases.

• Cell-Cell Communication: Mediate signaling and adhesion (receptors, gap junctions).

• Endocytosis and Exocytosis: Involved in vesicle formation and fusion.

• Targeting, Sorting, and Modification: Direct proteins to specific locations (ER, Golgi).

• Stabilizing and Shaping: Maintain membrane structure and integrity.

Asymmetrical Orientation of Membrane Proteins and Glycolipids

• Transmembrane proteins have a fixed orientation relative to membrane faces.

• Glycoproteins are always oriented with carbohydrate chains facing the exoplasmic (external) domain.

• Lipid-anchored and integral monotopic proteins are associated with one specific membrane surface.

N-linked and O-linked Glycosylation

Glycosylation is the process of attaching carbohydrate groups to proteins or lipids, critical for protein folding, stability, and cell recognition.

• N-linked glycosylation: Carbohydrate attaches to the nitrogen atom of an asparagine residue.

• O-linked glycosylation: Carbohydrate attaches to the oxygen atom of serine, threonine, or modified lysine/proline residues.