Membrane Structure and Function Overview

Membrane Structure, Function, and Chemistry

• Membranes are fundamental components of all biological systems, acting as boundary and permeability barriers.
• Membranes organize and localize functions, facilitating specialized processes within cells.
• Membranes play a role in transport, signal detection, and cell-to-cell interactions.
• The fluid mosaic model describes membranes as two fluid layers of lipids with proteins embedded within and on the layers.
• Key experiments contributed to understanding membrane structure and function.

Overton's Contribution

• Overton (1890s) observed that lipid-soluble substances readily penetrate cells, leading to the conclusion that cell surfaces contain lipids.

Langmuir's Contribution

• Langmuir (1900) found that phospholipids, which are amphipathic (having both hydrophilic and hydrophobic regions), form a single molecule layer on water surfaces.

Gorter and Grendel's Contribution

• Gorter and Grendel (1925) extracted lipids from red blood cells and measured their surface area on water.
• Their findings supported the lipid bilayer model, as the measured area was twice the surface area of the red blood cells.
• The most favorable structure for lipids was a lipid bilayer with nonpolar regions facing inward.

Davson and Danielli's Contribution

• Davson and Danielli (1940) proposed that membranes contain a lipid bilayer with protein layers on both sides.

Problem with the Davson-Danielli Model

• Isolated membrane proteins have shapes and sizes inconsistent with a monolayer protein model.
• Protein-to-lipid ratios vary among different membranes.
• Phospholipases easily degrade membrane phospholipids.

The Singer-Nicholson Fluid Mosaic Model

• The fluid mosaic model accounts for all inconsistencies with previous models and envisions a mobile bilayer of lipids with embedded or attached proteins.

Unwin and Henderson's Contribution

• Unwin and Henderson (1980) determined that integral membrane proteins often contain segments spanning the lipid bilayer, mainly in the form of alpha helices.

Membrane Lipids: The "Fluid" Part

• Membrane lipids, including phospholipids, glycolipids, and sterols, are integral components of the membrane's “fluid” part.

Phospholipids

• Phospholipids are the most abundant membrane lipids, and are comprised of glycerol-based phosphoglycerides and sphingosine-based sphingolipids.
• Composition varies in membranes from various origins.

Glycolipids

• Glycolipids are formed from the addition of carbohydrates to lipid.
• They may be derived from glycerol or sphingosine.
• Examples include cerebrosides and gangliosides.

Sterols

• Membranes of most eukaryotes have significant amounts of sterols.
• Cholesterol is the main sterol for animal cell membranes, stabilizing and maintaining cell membranes.

Membrane Asymmetry

• Membrane asymmetry refers to the unequal distribution of lipids between the membrane's two layers.
• Most glycolipids in animal cells reside in the outer layer.
• Asymmetry is established during membrane synthesis.

Lipid Movement

• Lipids within their monolayer can rotate and diffuse laterally.
• Transverse diffusion ("Flip-flop") is relatively rare due to the hydrophobic nature of the membrane interior.

Measuring Lipid Mobility

• Fluorescence recovery after photobleaching (FRAP) measures the rate of lipid diffusion in membranes by labeling lipids with fluorescent dyes.

Membrane Fluidity

• Membrane fluidity is regulated by factors such as temperature, fatty acid structure, and sterol incorporation.
• Unsaturated fatty acids and decreased hydrocarbon tail length generally increase membrane fluidity.
• Sterols can decrease membrane fluidity at higher temperatures.

Membrane Proteins: The "Mosaic" Part

• The mosaic part of the model involves mainly membrane proteins, along with lipid rafts and other lipid domains.

Classes of Membrane Proteins

• Integral membrane proteins are embedded in the bilayer due to their hydrophobic regions.
• Peripheral proteins are hydrophilic and located on the membrane surfaces.
• Lipid-anchored proteins are attached to the bilayer by covalent attachments to lipids.

Membrane Protein Orientation

• Membrane proteins exhibit asymmetric orientation across the lipid bilayer.
• Proteins' positions are fixed once placed in or on one of the membrane layers, to prevent their movement across the membrane.

Glycoproteins

• Many membrane proteins are glycosylated, meaning they have carbohydrate chains covalently attached. This glycosylation occurs in the endoplasmic reticulum and Golgi compartments.

Glycosylation Types

• N-linked glycosylation is linked to the nitrogen atom in an asparagine residue.
• O-linked glycosylation is linked to the oxygen atom in a serine, threonine, or modified lysine or proline residue.

Carbohydrate Chains

• Attached carbohydrate chains to peptides can either be straight or branched, with lengths varying from 2 to 60 sugar units.
• Common sugars include galactose, mannose, N-acetylglucosamine, and sialic acid.