Rucete ✏ Lehninger Principles of Biochemistry In a Nutshell
11.1 The Composition and Architecture of Membranes
This chapter explains how biological membranes are built from lipids and proteins, how their structure supports cellular function, and how membranes are organized dynamically inside cells.
The Lipid Bilayer Is Stable in Water
• Biological membranes are mainly composed of glycerophospholipids, sphingolipids, and sterols such as cholesterol.
• These lipids are amphipathic, meaning they contain both hydrophobic (water-repelling) and hydrophilic (water-attracting) regions.
• In water, membrane lipids spontaneously arrange themselves so that hydrophobic tails avoid water while hydrophilic heads contact water.
• This self-assembly is driven by the hydrophobic effect, which reduces ordered water molecules around exposed hydrophobic surfaces and increases entropy.
• The hydrophobic effect is not a true chemical bond. Instead, molecules move into the lowest-energy arrangement in water.
• Depending on lipid shape and conditions, amphipathic lipids can form several structures.
Micelles
• Micelles are spherical aggregates containing dozens to thousands of amphipathic molecules.
• Hydrophobic tails cluster in the center, while hydrophilic heads face outward toward water.
• Micelles are favored when the head group is larger than the tail region.
• Examples include free fatty acids, lysophospholipids, and detergents such as sodium dodecyl sulfate (SDS).
Bilayers
• Bilayers form when head groups and tails have similar cross-sectional areas.
• Glycerophospholipids and sphingolipids commonly form bilayers.
• Two monolayers, called leaflets, arrange so hydrophobic tails face inward and hydrophilic heads face water on both sides.
• Open bilayer sheets are unstable because exposed edges contact water.
• Therefore, bilayers spontaneously curve and close into vesicles or liposomes.
Vesicles and Liposomes
• Vesicles are hollow spheres formed from closed lipid bilayers.
• Closing the bilayer eliminates exposed hydrophobic edges and increases stability.
• Vesicles create a separate internal aqueous compartment called the lumen.
• Primitive cells may have resembled simple lipid vesicles enclosing aqueous contents.
Physical Properties of Bilayers
• The hydrocarbon core of the bilayer is highly nonpolar, similar to decane.
• It is about 3 nm thick, roughly the width of two extended fatty acid chains.
• Real biological membranes are about 50–80 Å thick when proteins protruding from both sides are included.
Bilayer Architecture Underlies Biological Membrane Function
• In membranes, phospholipids form a bilayer with proteins embedded within it.
• Hydrophobic protein regions contact the fatty acid tails of lipids.
• Some proteins project from one side only, while others span the membrane and project from both sides.
• Membranes are asymmetric, meaning the two sides differ in lipid and protein composition.
• This asymmetry gives membranes functional sidedness.
• Membranes follow the fluid mosaic model.
• Lipids and proteins move laterally within the membrane plane while the barrier function remains intact.
Membranes Are Dynamic Structures
• Membranes are not passive walls.
• They are flexible, self-repairing, and selectively permeable.
• Flexibility allows shape changes during growth and movement such as amoeboid motion.
• Membranes can break and reseal during membrane fusion or fission.
• Fusion occurs in exocytosis.
• Fission occurs in endocytosis and cell division.
• Selective permeability allows membranes to control movement of molecules.
Roles of Membrane Proteins
• Transporters move ions and organic molecules across membranes.
• Receptors detect extracellular signals and initiate cellular responses.
• Ion channels mediate electrical communication between cells.
• Adhesion molecules connect neighboring cells.
• Enzymes located in membranes catalyze important reactions.
Lipid-to-Protein Ratios Vary
• Different membranes contain different proportions of lipid and protein depending on function.
• Myelin membranes are rich in lipid and act as electrical insulators around neurons.
• Bacterial membranes and mitochondrial or chloroplast membranes contain more protein because many enzymes are located there.
Membranes Organize Cellular Processes
• Inside cells, membranes help organize lipid synthesis, protein synthesis, and energy conversion.
• Membrane proteins move in two dimensions, increasing the chance of collisions between enzymes and substrates.
• This can greatly improve metabolic efficiency.
The Endomembrane System Is Dynamic and Specialized
• In eukaryotic cells, the endoplasmic reticulum (ER), Golgi apparatus, lysosomes, and transport vesicles are each surrounded by single membranes.
• The nucleus, mitochondria, and chloroplasts contain double membranes.
• Together these structures form the endomembrane system.
• The ER is highly dynamic and forms tubules and sheets throughout the cell.
• Organelles remain separate compartments but exchange lipids and proteins actively.
Membrane Trafficking
• Most membrane lipids and proteins are synthesized in the ER.
• Vesicles bud from the ER and fuse with the cis Golgi.
• Materials move through the Golgi to the trans side.
• During Golgi passage, proteins and lipids undergo covalent modifications.
• Some modifications act like molecular ZIP codes that direct final destination.
Distinct Lipid Composition of Organelles
• Each species, tissue, cell type, and organelle has a characteristic membrane lipid composition.
• Plasma membranes are rich in cholesterol and sphingolipids.
• Plasma membranes contain essentially no cardiolipin.
• Mitochondrial membranes contain little cholesterol or sphingolipid.
• Mitochondria contain most cellular phosphatidylglycerol and cardiolipin.
• Cardiolipin is required for proper assembly of respiratory complexes.
• Many functional reasons for specific lipid mixtures are still unknown.
Asymmetry of Plasma Membranes
• The two leaflets of plasma membranes have different lipid compositions.
• Outer leaflet commonly contains phosphatidylcholine and sphingomyelin.
• Inner leaflet contains phosphatidylserine, phosphatidylethanolamine, and phosphatidylinositols.
• Negatively charged head groups on the inner leaflet interact with positively charged regions of membrane proteins.
Lipid Transfer Proteins (LTPs)
• Lipids also move between membranes through lipid transfer proteins.
• LTPs are soluble proteins with hydrophobic pockets that shield lipids while transporting them through cytosol.
• Some LTPs exchange one lipid for another, such as delivering cholesterol and returning with phosphatidylinositol.
• Some LTPs form hydrophobic tunnels between adjacent membranes.
• ATP may be required, often supplied through ABC transporters.
• Lipid transfer by LTPs can be faster than vesicle transport.
Fatty Acid Remodeling
• After reaching destination membranes, phospholipids may undergo enzymatic remodeling of fatty acid chains.
Membrane Proteins Are Receptors, Transporters, and Enzymes
• Membrane protein composition reflects membrane specialization.
• Many proteins receive extracellular signals such as hormones or voltage changes.
• Hundreds of transporters carry sugars, amino acids, vitamins, ions, and metabolites across membranes.
• Many receptors and transporters must span the membrane at least once.
• Some enzymes span membranes, while others act from one side only.
Protein Processing in the ER and Golgi
• Proteins destined for plasma membranes often undergo posttranslational modification.
• Glycosylation adds oligosaccharides to proteins.
• In glycophorin of red blood cells, about 60% of mass is carbohydrate.
• Sugars are commonly attached to Ser, Thr, or Asn residues.
• Carbohydrates always face the outer side of the plasma membrane.
• Some proteins are modified by covalent lipid attachment.
• These lipids anchor proteins to membranes or target them to specific locations.
Types of Membrane Protein Association
• Integral membrane proteins are firmly embedded in the bilayer.
• They can be removed only with detergents or organic solvents.
• Peripheral proteins bind through electrostatic interactions or hydrogen bonds.
• They can be released with mild treatments.
• Amphitropic proteins reversibly associate with membranes and can exist in cytosol or membrane.
Integral Protein Categories
• Monotopic proteins penetrate only one leaflet.
• Bitopic proteins cross the membrane once.
• Glycophorin is bitopic.
• Polytopic proteins cross the membrane multiple times.
• Each transmembrane α-helix usually contains about 20 hydrophobic residues.
Bacteriorhodopsin Example
• Bacteriorhodopsin is a seven-pass membrane protein.
• It acts as a light-driven proton pump in Halobacterium salinarum.
• Seven α-helices span the membrane and are connected by loops.
• This seven-helix motif is common in signal receptors.
Lipid Annuli Around Proteins
• Many membrane proteins crystallize with surrounding phospholipids.
• Lipid head groups interact with polar residues at membrane surfaces.
• Lipid tails contact hydrophobic protein surfaces.
• Lipids between subunits can form a sealing layer called a grease seal.
Predicting Membrane Protein Topology
• Topology means the orientation of a protein relative to the bilayer.
• Long stretches of more than 20 hydrophobic residues usually indicate transmembrane segments.
• About 20–30% of proteins in many organisms are integral membrane proteins.
• A 20–25 residue α-helix is long enough to span the membrane.
• In hydrophobic environments, helices or β-sheets maximize internal hydrogen bonding.
Hydropathy Analysis
• Each amino acid has a hydropathy index based on free-energy transfer between water and hydrophobic environments.
• Investigators scan sequences using moving windows of residues.
• Regions with high hydropathy across more than 20 residues are predicted membrane-spanning segments.
• Hydropathy plots correctly predict one helix in glycophorin and seven helices in bacteriorhodopsin.
β-Barrel Membrane Proteins
• Not all membrane proteins use α-helices.
• Many bacterial and mitochondrial outer membrane proteins form β-barrels.
• Multiple β-strands create a cylindrical structure surrounding a pore.
• Porins of gram-negative bacteria such as E. coli are β-barrel proteins.
• Outer membranes of mitochondria and chloroplasts also contain many β-barrel proteins.
• Only 7–9 residues in β-conformation are needed to span a membrane.
• In β-strands, alternating residues face opposite directions, so every second residue often contacts lipid.
Special Amino Acid Distribution
• Tyr and Trp residues often cluster at the lipid-water interface.
• They help anchor proteins at the membrane surface.
• Lys and Arg residues are more common on cytoplasmic loops of plasma membrane proteins.
• This pattern is called the positive-inside rule.
In a Nutshell
Biological membranes are dynamic lipid bilayers containing specialized proteins that control transport, signaling, catalysis, and compartmentalization. Membrane lipids self-assemble through the hydrophobic effect, while proteins are organized as integral, peripheral, or reversible associates. Different organelles maintain unique membrane compositions, and membrane protein topology can often be predicted from hydrophobic amino acid sequences.