Membranes - Structure and Function

Membranes: Structure and Function

Membrane Structure & Function

• The plasma membrane encloses the cell, defining the boundary of 'life'.
• It maintains essential differences between the cytosol and the external environment.
• Interior cell membranes compartmentalize the cell, enabling different parts to develop specific functions.
• Membranes form a relatively impermeable barrier, facilitating controlled access to the cell interior.
• Ion gradients are established by membrane-bound transporter molecules.
• These gradients drive:
  • ATP synthesis
  • Movement of selected solutes
  • Production and transmittance of electric signals
• The plasma membrane contains proteins that act as sensors to external signals, allowing cells to respond to environmental changes.
• These protein sensors/receptors transmit information across the membrane (signal transduction).
• The surface chemistry of the membrane is important in cellular recognition and processes like adhesion.
• Membrane chemistry can play a key role in resisting pathogens or allowing them access to the cell.

Cell Membranes: Composition & Structure

• Membranes are composed of phospholipids and proteins (50:50 ratio).
• Hydrophilic head groups face outwards, and hydrophobic tails face inwards.
• Lipid molecules form a bimolecular leaflet consisting of a 5nm thick double sheet of phospholipid molecules.
• Cell membranes are plastic and deformable.
• Cell membranes are fluid dynamic structures, with lipid molecules moving freely in the plane of the membrane (2 µms-1), though rarely flipping across it.

Membranes Are Fluid

• Protein molecules form complexes that float in a sea of lipid.
• Proteins also serve as structural links with the underlying cytoskeleton, which can anchor components and stabilize the membrane.

Phospholipid Component of Membranes

• Phospholipids are the most common membrane components.
• The polar head group consists of choline linked via a phosphate group to glycerol (C3).
• Two hydrophobic hydrocarbon tails are fatty acid chains, 12-34 carbons in length.
• One chain is fully saturated (straight), and the other is unsaturated with one or more cis double bonds (giving the molecule a kinked profile).
• Lipids constitute 50% of the mass of the membrane, with $5 \times 10^6$ molecules per square µm.
• Lipids are amphipathic, with hydrophobic and hydrophilic ends.

Properties of Phospholipids

• In water, phospholipid molecules aggregate with their hydrophobic tails buried inwards and their hydrophilic heads exposed to water (micelles).
• They typically form biomolecular sheets, which form 'liposomes' separating two aqueous phases.
  • Outside:
    • Glycolipids
    • Phosphatidyl choline
    • Sphingomyelin
  • Inside:
    • Phosphatidylethanolamine
    • Phosphotidylserine (negatively charged).
• This results in charge asymmetry.

Membrane Asymmetry

• Flippase:
  • Enzyme that moves phospholipids from the inner (lumen) to the outer-facing monolayer (cytosolic).
  • Different flippases for different phospholipids help establish asymmetry.
• Floppase:
  • Enzyme found in the cell membrane.
  • Moves phospholipids from the cytosolic facing to the inside facing.
• Scramblase:
  • Ensures even numbers of phospholipids on either side of the bilayer by random transfer from one monolayer to the other.

Other Membrane Components - Glycolipids

• Sugar-containing lipid molecules, constituting around 5% of plasma membrane lipids.
• Sugar groups are oriented towards the outside of the cell and are exposed at the cell surface.
• The most complex are gangliosides, which have attached oligosaccharides.
• These are important components of the surface of nerve cells (10% lipid).
• Ganglioside GM1 acts as a surface receptor for the bacterial toxin that causes cholera.

Membrane Manufacture

• Glycolipids use a different mechanism to be asymmetrically localized; there are no glycolipid flippases.
• The enzyme that adds sugar groups on phospholipids is on the inner face of the Golgi apparatus.
• Fusion of vesicle budded off Golgi keeps internal face outside cell – the cytosol face is maintained!

Other Membrane Components - Cholesterol

• The eukaryote cell plasma contains large amounts of cholesterol.
• It makes membranes less permeable.
• Cholesterol molecules orient themselves in the bilayer with hydroxyl heads close to polar groups of lipid, partially immobilizing phospholipid molecules.
• It makes the membrane less deformable.
• It also acts as a spacer, preventing phase transitions ('freezing' of membranes).

Fluid Properties of Phospholipid Membranes

• The fluidity of cell membranes depends on their biochemical composition.
• Shorter chain lengths of fatty acids reduce the tendency of hydrocarbon tails to interact with each other.
• Cis-double bonds produce kinks, making molecules less likely to pack closely together, and allow cholesterol to fit snugly between.
• This enables membranes to remain fluid at lower temperatures.
• Organisms adjust the composition of their membrane lipids to maintain constant fluidity with changing temperature. As temperatures fall, the proportion of lipids with cis bonds increases.

Membrane Proteins

• The amount and types of proteins associated with membranes are highly variable.
• In myelin membrane, serving to insulate nerve cells, less than 25% of mass is protein.
• In membranes involved in energy transduction processes, like the inner membrane of the mitochondrion, nearly 75% is protein.
• Membrane proteins often have oligosaccharide chains attached, particularly the plasma membrane.
• The outer surface is coated by a layer of carbohydrate, forming the glycocalyx.

Glycocalyx

• A carbohydrate-rich zone on the cell surface.
• Oligosaccharides mainly associated with proteins, although some are glycolipids.
• Selectins are cell surface binding proteins that mediate cell-cell adhesions.
• These sugars provide surface markers used to identify cells (e.g., by potential pathogens or opposite mating types).

Functions of Integral Membrane Proteins

• The lipid bilayer provides a selective barrier; membrane proteins are needed to:
  • Transport nutrients, ions, and metabolites
  • Anchor the membrane to macromolecules
  • Detect external signals
  • Serve as enzymes to carry out specific reactions

Structural Proteins Associated with the Inside of Red Blood Cell Membrane

• Spectrin is associated with the cytoplasmic side of membranes.
• Ankyrin links spectrin to transmembrane proteins and binds the 'skeleton' to the inner face of the membrane.
• This gives red blood cells their characteristic shape.

Protein - Membrane Associations

• (A) Transmembrane
• (B) Monolayer-Associated
• (C) Lipid-Linked
• (D) Protein-Attached

Getting Into and Out of Cells

• Involves Transporter molecules and Lysosomes

Membrane Permeability

• Protein-free lipid bilayers are highly impermeable to ions.
• The smaller the molecule and the more soluble it is in oil, the more rapidly it will diffuse across such bilayers.
• Small nonpolar gas molecules such as $O<em>2$ and $CO</em>2$ rapidly diffuse across lipid bilayers (i.e., can move easily into and out of cells).
• Uncharged polar molecules can also diffuse quickly if they are small enough – e.g., water, ethanol, urea.
• Larger molecules such as glucose hardly diffuse at all.
• Membranes are virtually impermeable to charged molecules irrespective of size; ions such as $K^+$ and $Na^+$ hardly move across membranes.

Proteins Facilitate Movement

• Proteins in membranes facilitate the movement of molecules that cannot diffuse passively through membranes: Carrier vs Channel Proteins
• Carrier protein: alternates between two conformations, so the binding site is subsequently available on one side of the membrane and then the other.
• Channel protein: forms a water-filled pore across the bilayer through which ions can diffuse. Can be opened and shut by a variety of mechanisms.

Opening and Closing of Channel Proteins

• (A) Voltage-gated
• (B) Ligand-gated (extracellular ligand)
• (C) Ligand-gated (intracellular ligand)
• (D) Stress-gated

Mechanisms of Movement Across Membranes

• Passive – down an electrochemical gradient
• Active – up an electrochemical gradient.

Molecules Bind to Carrier Protein

• Molecules bind to a carrier protein and cause it to change conformation.
• Illustrates a carrier protein mediating facilitated diffusion along an electrochemical gradient.

3 Types of Carrier Proteins