Membrane Structure and Function Notes

Membranes

Plasma Membrane

• The plasma membrane is an asymmetric fluid mosaic.
• It features a lipid bilayer with a hydrophobic core and hydrophilic surfaces.
• Integral proteins are embedded in the membrane, often spanning it entirely (transmembrane).
• Peripheral proteins are loosely bound to the membrane surface.
• Carbohydrate chains of glycoproteins and glycolipids are found on the extracellular surface.

Membrane Flexibility

• Membranes are flexible and dynamic.

Phospholipid Bilayer

• Phospholipids form the membrane bilayer.
• Hydrophilic polar head groups face outward on both sides of the membrane.
• Hydrophobic fatty acid chains are internal to the membrane.

Amphipathic Lipids

• Membranes are mixtures of amphipathic lipids.
• Phosphoglycerides have varied polar head groups.
• Sphingolipids include sphingomyelin and glycolipids.

Membrane Asymmetry

• Plasma membranes are asymmetric.
• The outer leaflet contains more phosphatidylcholine and sphingomyelin, as well as glycolipids.
• The inner leaflet contains more phosphatidylserine (charged) and phosphatidylethanolamine.

Fatty Acids and Membrane Packing

• Membrane lipids contain a mixture of different fatty acid species.
• Fatty acids containing cis double bonds are kinked and cannot pack as closely as saturated fatty acids.
• The greater the number of double bonds, the more fluid the membrane.

Fluid Mosaic Model

• Phospholipids can move within the lipid bilayer.
• They can diffuse laterally, bend (flex), and rotate.
• Spontaneous movement from one leaflet to the other (flip-flop) is rare.
• Flippases are special proteins that contribute to the synthesis of asymmetric membranes.

Cholesterol in Membranes

• Mammalian plasma membranes contain cholesterol.
• Cholesterol is mostly hydrophobic, except for one hydroxyl group.
• Cholesterol stiffens the region of the membrane adjacent to the sterol ring, 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 pass completely through the membrane and have hydrophilic portions on both sides.
• Peripheral proteins are not embedded in the membrane and can be solubilized by aqueous solvents, such as high salt buffers.

Functions of Integral Membrane Proteins

• Transporters: Facilitate the movement of molecules across the membrane.
• Anchors: Link the membrane to other structures.
• Receptors: Bind to signaling molecules.
• Enzymes: Catalyze reactions at the membrane.

Transmembrane Proteins

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

Types of Transmembrane Proteins

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

Hormone Receptors

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

Partially Embedded Proteins

• A few proteins are embedded in the membrane but do not span the entire membrane.
• Cyclooxygenase-1, which catalyzes the synthesis of prostaglandins, is one such protein.
• The alpha-helices embedded in the membrane have hydrophobic side chains.

Lipid-Anchored Proteins

• Some proteins have lipids attached to them after they are synthesized, anchoring them to the membrane.
• Proteins can be anchored to either the intracellular or extracellular surface.

Lipid Anchors

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

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

• Some proteins are normally cytosolic.
• Specific intracellular signals can result in modification of the protein so that it is found associated with the membrane.
• Protein kinase C binds the lipid diacylglycerol, which serves to anchor it to the membrane.
• Phospholipase A2 is phosphorylated, which enhances 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 have primarily saturated hydrocarbon chains.
• Association of cholesterol leads to domains that are in an ordered lipid state.
• Caveolae and rafts contain specific proteins which contribute to membrane functions, such as:
  • Intracellular signaling (protein kinase C)
  • Extracellular signal reception (LDL receptor)
  • Catalysis (endothelial nitric oxide synthase)

Movement of Membrane Proteins

• Many membrane proteins can move laterally within the fluid lipid bilayer.
• Movement of membrane proteins can be visualized by forming heterokaryons. With time, the two groups of proteins (with different fluorescent tags) become intermixed.

Restricted Protein Movement

• Some integral proteins are linked to peripheral cytoplasmic proteins of the cytoskeleton.
• Cytoplasmic proteins anchor the membrane proteins and limit their lateral movement.

Tight Junctions

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

FRAP (Fluorescence Recovery After Photobleaching)

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

Glycocalyx

• The cell coat 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 the proteins, glycoproteins, and proteoglycans which make up the extracellular matrix.