Biological Membranes and the Cell Surface

Membrane Structure According to the Fluid Mosaic Model of Singer and Nicolson

The membrane is a fluid mosaic of phospholipids and proteins Two main categories of membrane proteins - integral and peripheral Peripheral proteins - bound to the surface of the membrane Integral proteins - permeate the surface of the membrane Membrane regions differ in protein configuration and concentration Outside vs. inside - different peripheral proteins Proteins only exposed to one surface Proteins extend completely through - exposed to both surfaces Membrane lipid layer fluid Proteins move laterally along membrane

Membrane Lipids

• Phospholipids most abundant
  • Phosphate may have additional polar groups such as choline, ethanolamine, serine, inositol
  • These increase hydrophilicity
• Cholesterol - a steroid
  • Can comprise up to 50% of animal plasma membrane
  • Hydrophilic OH groups toward surface
  • Smaller than a phospholipid and less amphipathic (having both polar and non-polar regions of the molecule)
• Other molecules include ceramides and sphingolipds - amino alcohols with fatty acid chains
• These lipids distributed asymmetrically

Bilayer Formation

• Membrane components are Amphipathic (having both polar and non-polar regions of the molecule)
• Spontaneously form bilayers
  • Hydrophilic portions face water sides
  • Hydrophobic core
• Never have a free end due to cohesion
  • Spontaneously reseal
  • Fuse
• Liposome - Circular bilayer surrounding water compartment
  • Can form naturally or artificially
  • Can be used to deliver drugs and DNA to cells

Membrane Fluidity

• Membrane is Fluid
• Lipids have rapid lateral movement
• Lipids flip-flop extremely slowly
• Lipids asymmetrically distributed in membrane
  • Different lipids in each side of bilayer
• Fluidity depends on lipid composition
  • Saturated fatty acids
    • All C-C bonds are single bonds
    • Straight chain allows maximum interaction of fatty acid tails
    • Make membrane less fliuid
    • Solid at room temperature
    • "Bad Fats" that clog arteries (animal fats)
  • Unsaturated fatty acids
    • Some C=C bond (double bonds)
    • Bent chain keeping tails apart
    • Make membrane more fluid
    • Polyunsaturated fats have multiple double bonds and bends
    • Liquid at room temperature
    • "Good Fats" which do not clog arteries (vegetable fats)
  • Cholesterol
    • Reduces membrane fluidity by reducing phospholipid movement
    • Hinders solidification at low (room) temperatures

How Cells Regulate Membrane Fluidity

• Desaturate fatty acids
• Produce more unsaturated fatty acids
• Change tail length (the longer the tail, the less fluid the membrane)

Membrane Carbohydrates - Glycolipids and Glycoproteins

• Face away from cytoplasm (on outside of cell)
• Attached to protein or lipid
  • Blood antigens - Determine blood type - bound to lipids (glycolipids)
  • Glycoproteins - Protein Receptors
  • Provide specificity for cell-cell or cell-protein interactions (see below)

Membrane Proteins

• Peripheral Proteins
  • completely on membrane surface
  • ionic and H-bond interactions with hydrophilic lipid and protein groups
  • can be removed with high salt or alkaline
• Integral Proteins
  • Possess hydrophobic domains which are anchored to hydrophobic lipids
  • alpha helix
  • more complex structure

An Example - Asymetry of Intestinal Epithelial Cell Membranes

• Apical surface selectively absorbs materials
  • Contains specific transport proteins
• Lateral surface interacts with neighboring cells
  • Contains junction proteins to allow cellular communication
• Basal surface sticks to extracellular matrix and exchanges with blood
  • Contains proteins for anchoring

The Extracellular Matrix (ECM) and Plant Cell Walls

• In animal cells, the ECM is a mish-mash of proteins (usually collagen) and gel-forming polysaccharides
• The ECM is connected to the cytoskeletin via Integrins and Fibronectins
• Plant Primary Cell Walls for a rigid cross-linked network of cellulose fibers and pectin - a fiber composite
  • Fiber composites resist tension and compression
• Plant Secondary Cell Walls are further strengthened w/ Lignin
  • Secondary Cell Walls is basically what comprises wood

Cell to Cell Attachments

Tight Junctions and Desmosomes

• Tight Junctions are specialized proteins in the plasma membranes of adjacent animal cells
  • they "stitch together" adjacent cells
  • form a watertight cell
• Desmosomes are specialized connection protein complexes in animal cells
  • they "rivet" cells together
  • they are attached to the intermediate fibers of adjacent cells

Cell Gaps

Plasmodesmata & Gap Junctions

• In plant cells, Plasmodesmata are gaps in the cell wall create direct connections between adjacent cells
  • May contain proteins which regulate cell to cell exchange
  • form a continuous cytoplasmic connection between cells called the symplast
• In animal cells, Gap Junctions are holes lined with specialized proteins
  • allow cell-cell communication (this is what coordinates your heartbeat)

Cell Communication

In multi-cellular organism, cells can communicate via chemical messenger

Three Stages of Cellular Communication

• Reception
  • A chemical message (ligand) binds to a protein on the cell surface 
• Transduction
  • The binding of the signal molecule alters the receptor protein in some way.
  • The signal usually starts a cascade of reactions known as a signal transduction pathway
• Response
  • The transduction pathway finally triggers a response
  • The responses can vary from turning on a gene, activating an enzyme, rearranging the cytoskeleton
  • There is usually an amplification of the signal (one hormone can elicit the response of over 10⁸ molecules

No matter where they are located, signal receptors have several general characteristics

• signal receptors are specific to cell types (i.e. you won't find insulin receptors on bone cells)
• receptors are dynamic 
  • the number of receptors on a cell surface is variable
  • the ability of a molecule to bind to the receptor is not fixed (i.e. it may decline w/ intense stimulation)
• receptors can be blocked

Two Methods of Cell-Cell Communication

• Steroid Hormones can enter directly into a cell
  • bind to receptors in the cytosol
  • hormone-receptor complex binds to DNA, inducing change
  • testosterone, estrogen, progesterone are examples of steroid hormones
• Signal Transduction - conversion of signals from one form to another
  • Very complicated pathways - all are different!
  • G Protein receptors
    • G-proteins are called as such because they have GTP bound to them
    • Receptors have inactive G-proteins associated with them
    • When the signal binds to the receptor, the G-protein changes shape and becomes active (into the "on configuration)
    • The active G-protein binds to an enzyme which produces a secondary message
    • Frequently, second messengers activate other messengers, creating a cascade...
  • G-protein signal transduction sequences are extremely common in animal systems
    • embryonic development
    • human vision and smell
    • over 60% of all medications used today exert their effects by influencing G-protein pathways
  • Tyrosine-Kinase Receptors - Another Example of a Signal Transduction Pathway
    • Tyrosine-Kinase Receptors often have a structure similar to the diagram below:
    • Part of the receptor on the cytoplasmic side serves as an enzyme which catalyzes the transfer of phosphate groups from ATP to the amino acid Tyrosine on a substrate protein
    • The activation of a Tyrosine-Kinase Receptor occurs as follows:
      • Two signal molecule binds to two nearby Tyrosine-Kinase Receptors, causing them to aggregate, forming a dimer
      • The formation of a dimer activated the Tyrosine-Kinase portion of each polypeptide
      • The activated Tyrosine-Kinases phosphorylate the Tyrosine residues on the protein
    • The activated receptor protein is now recognized by specific relay proteins
    • They bind to the phosphorylated tyrosines, which cause, you guessed it, a conformation change.
    • The activated relay protein can then trigger a cellular response
      • One activated Tyrosine-Kinase dimer can activate over ten different relay proteins, each which triggers a different response
      • The ability of one ligand binding event to elicit so many response pathways is a key difference between these receptors and G-protein-linked receptors (that, and the absence of G- proteins of course...)
      • Abnormal Tyrosine-Kinases that aggregate without the binding of a ligand have been linked with some forms of cancer
• Signal Transduction Shutdown
  • Most signal-transduction/hormone systems are designed to shut down rapidly
  • Enzymes called phosphatases remove the phosphate groups from secondary messengers in the cascade
  • This will shut down the signal transduction pathway... at least until another signal is received