Membrane Structure and Function Notes

Membranes

Plasma Membrane Structure

• The plasma membrane is an asymmetric fluid mosaic.
• It features a lipid bilayer with a hydrophobic core and hydrophilic surfaces.
• Integral proteins are embedded within the membrane, often spanning its entire width (transmembrane).
• Peripheral proteins are loosely associated with the membrane surface.
• Carbohydrate chains of glycoproteins and glycolipids are located on the extracellular surface.

Membrane Flexibility

• Membranes possess flexibility and are dynamic structures.

Phospholipid Bilayer

• Phospholipids form the basic structure of the membrane bilayer.
• Hydrophilic polar head groups face outward, interacting with the aqueous environment on both sides of the membrane.
• Hydrophobic fatty acid chains are oriented inward, forming the core of the membrane.

Amphipathic Lipids

• Membranes comprise mixtures of amphipathic lipids.
• Phosphoglycerides have varying polar head groups.
• Sphingolipids, including sphingomyelin and glycolipids, are also present.

Membrane Asymmetry

• Plasma membranes exhibit asymmetry in lipid composition.
• The outer leaflet is enriched in phosphatidylcholine, sphingomyelin, and glycolipids.
• The inner leaflet contains more phosphatidylserine (negatively charged) and phosphatidylethanolamine.

Fatty Acids and Membrane Packing

• Membrane lipids contain a variety of different fatty acid species.
• Cis double bonds in fatty acids create kinks, preventing close packing compared to fully saturated fatty acids.
• A greater number of double bonds increases membrane fluidity.

Fluid Mosaic Model

• Phospholipids can move laterally within the lipid bilayer.
• They can also undergo bending (flexion) and rotation.
• Spontaneous flip-flop (movement from one leaflet to the other) is rare.
• Flippases are special proteins that facilitate the synthesis of asymmetric membranes by catalyzing the flip-flop of certain phospholipids.

Cholesterol in Membranes

• Mammalian plasma membranes contain cholesterol.
• Cholesterol molecules are largely hydrophobic, with only one hydroxyl group.
• Cholesterol stiffens the region of the membrane adjacent to the sterol ring, thereby strengthening the membrane.
• The middle section of the bilayer remains relatively more fluid.

Membrane Proteins

• Integral membrane proteins are embedded in the bilayer and can only be removed with detergents.
• Most integral proteins pass entirely through the membrane, possessing hydrophilic portions on both sides.
• Peripheral proteins are not embedded in the membrane.
• They can be solubilized using aqueous solvents like high salt buffers.

Integral Membrane Protein Functions

• Integral proteins perform diverse functions:
  • Transporters: Facilitate the movement of molecules across the membrane.
  • Anchors: Connect the membrane to other structures.
  • Receptors: Bind to signaling molecules.
  • Enzymes: Catalyze reactions at the membrane.

Transmembrane Proteins

• Many transmembrane integral proteins contain a segment with an alpha-helical structure, composed of amino acids with nonpolar side chains.
• Oligosaccharide chains and disulfide bonds are located on the non-cytosolic (outer) surface of the membrane.

Multiple-Pass Transmembrane Proteins

• Some proteins pass through the membrane multiple times.
• The hydrophobic portions can be alpha-helices or beta-pleated sheets.

Seven-Spanning Domain Receptors

• Many hormone receptors, particularly those linked to G proteins, have seven transmembrane domains.
• Examples include receptors for epinephrine and glucagon.

Partially Embedded Proteins

• A subset of proteins is embedded in the membrane but does not span its entire width.
• Cyclooxygenase-1, which catalyzes prostaglandin synthesis, is an example.
• Alpha-helices embedded in the membrane have hydrophobic side chains.

Lipid Anchors

• Lipids can be attached to proteins after their synthesis, anchoring them to the membrane.
• Proteins can be anchored to either the intracellular or extracellular surface.
• Some integral proteins contain covalently attached lipids.

Types of Lipid Anchors

• Some anchors are long hydrocarbon chains of:
  • Fatty acids: Myristate (14:0) or palmitate (16:0)
  • Poly-prenyl groups such as farnesyl
  • Some anchors are glycolipids, such as GPI (Glycosylphosphatidylinositol).

Peripheral Proteins

• Peripheral proteins are bound to the membrane by non-covalent interactions with other proteins.
• They are found on both the cytosolic and extracellular surfaces of the plasma membrane.

Protein Translocation

• Normally cytosolic proteins can associate with the membrane following specific intracellular signals.
• Protein kinase C binds to the lipid diacylglycerol, anchoring it to the membrane.
• Phospholipase A2 is phosphorylated, enhancing its binding to specific integral membrane proteins.

Specialized Membrane Domains

• Caveolae and rafts are specialized membrane domains rich in cholesterol and sphingolipids.
• Sphingomyelin and glycosphingolipids primarily have saturated hydrocarbon chains.
• Association of cholesterol leads to the formation of ordered lipid state domains.
• Caveolae and rafts contain specific proteins contributing to membrane functions:
  • Intracellular signaling (e.g., protein kinase C)
  • Extracellular signal reception (e.g., LDL receptor)
  • Catalysis (e.g., endothelial nitric oxide synthase)

Movement of Membrane Proteins

• Many membrane proteins can move laterally within the fluid lipid bilayer.
• Movement can be visualized using heterokaryons, where proteins with different fluorescent tags intermix over time.

Restricted Protein Movement

• Some integral proteins are linked to peripheral cytoplasmic proteins of the cytoskeleton.
• Cytoplasmic proteins anchor membrane proteins, limiting their lateral movement. This is seen in red blood cell membranes.

Tight Junctions

• Tight junctions between epithelial cells restrict the movement of plasma membrane proteins to specific membrane domains.

Fluorescence Recovery After Photobleaching (FRAP)

• FRAP is used to visualize protein movement within a membrane.
• FRAP can determine which proteins are free to move and which are anchored.

Glycocalyx

• The cell coat (glycocalyx) is rich in carbohydrates.
• Oligosaccharide chains are found on both membrane glycoproteins and glycolipids.
• Both integral and peripheral glycoproteins contribute to the glycocalyx.

Extracellular Matrix

• The glycocalyx is associated with proteins, glycoproteins, and proteoglycans that form the extracellular matrix.