Exam 3 Lecture Notes

Chapter 11: Cell Membranes

Membrane Structure

All cells have them.

• Prokaryotes: 1 membrane → the cytoplasmic membrane (plasma membrane)

• Eukaryotes: Multiple membranes → cytoplasmic membrane + all the various internal membranes (membrane-bound organelles)

General Properties

1. Fluid

   • Able to change shape very easily; flexible. Individual components that make up the membrane are usually free to move around in various ways.

   • Ex: Fibroblasts - Assume these really extreme angles.

   • Self-annealing.

2. Selectively Permeable

   • Selective about which molecules they allow to permeate the membrane.

   • How they maintain certain chemical environments.

3. Mosaics

   • Mixtures of different kinds of molecules (lipids, proteins, carbohydrates, etc.)

   • Ex: Human RBC, plasma membrane

     • ~43% lipids by weight

     • ~49% proteins by weight

     • ~8% carbohydrates by weight

   • Ex: Human neuron, plasma membrane

     • ~79% lipids

     • ~18% proteins

     • ~3% carbohydrates

4. Asymmetric

   • The two halves of the bilayer are chemically distinct; two layers with different compositions.

     • Cytoplasmic side (inner side)

     • Non-cytoplasmic side (outer layer)

       • AKA the luminal side

       • AKA the extracellular side

Components of Cell Membranes

1. Phospholipids

   • Primary structural components

   • Amphipathic (partially hydrophilic and partially hydrophobic)

     • Head: choline, phosphate, glycerol, polar, charged; Hydrophobic: Fatty acid chains, nonpolar, uncharged.

   • Spontaneously form a bilayer in water

     • If enough of them, they will seal off and form a ring (artificial cell membranes/liposomes).

   • Usually free to move around in various ways within one half of the bilayer

     • If they have any thermal energy: Flexion, which is the movement of the tails

     • Rotation is rotating on their axis/tails spin on head

     • Lateral Diffusion = drifting

     • Flipping = Rarely occurs, but means a phospholipid could jump from one half to the other half of a bilayer

   • New phospholipids are made in the luminal space of the endoplasmic reticulum

     • “Scramblases” - Scramble, or randomly distribute, the phospholipids from one monolayer to another

   • Golgi apparatus is where phospholipid asymmetry is generated

     • “Flippases” - Catalyzes the transfer of specific (scrambled) phospholipids to the cytosolic monolayer

   • One fatty acid hydrocarbon tail is straight (saturated) and one is kinked or bent (unsaturated)

     • Saturated: No double bonds (flexible)

     • Unsaturated: Have one or more double bonds (rigid, more inflexible) which causes kinks

       • This reduces/eliminates the possibility of “phase separation”

         • If both tails were saturated (straight), there would be less fluidity but the membrane would be easier to freeze (lose transport capacity and ability to transport vesicles).

         • If both tails were unsaturated (kinked), the membrane would be more fluid or even too flexible. It would also be harder to freeze.

         • Overall, this causes congregations/patches of phospholipids that freeze unevenly.

   • Ex: phosphatidylcholine

     

2. Glycolipids

   • Secondary structural & functional components

   • Ex: Galactocerebroside - In neuron plasma membranes

     

3. Cholesterol

   • Secondary structural component in animal cell membranes mainly

     • Affects membrane fluidity (more cholesterol = less flexible; less cholesterol = more flexible)

     • Able to relieve tension in the membrane by flipping

       • This is why cholesterol is so abundant in animal cells and not so much in plant cells—animal cells are exposed to much more extreme bending and movement

     

4. Proteins & Glycoproteins

   • Primary functional components (not so much structural)

   • Integral Membrane Proteins

     • Proteins that are integrated directly into the phospholipid bilayer

     • Transmembrane proteins

       • Span across/embedded in both halves of the bilayer

     • Membrane-associated proteins

       • Embedded in only one half of the bilayer

     • Lipid-linked proteins

       • Covalently attached to lipids that are part of one half of the bilayer

   • Peripheral Membrane Proteins

     • Noncovalently associated with integral membrane proteins

     • Signal transduction proteins and kinases

   • Functionally:

     • Transport

     • Receptors (hormone, cytokine, growth factor)

     • Enzymes (in mitochondria involved in cellular respiration

     • Recognition

   • Up to 50% of membrane by weight

     

5. Carbohydrates

   • Attached to membrane lipids (glycolipids) + attached to membrane proteins (glycoproteins) → form the glycocalyx (outer layer of carbohydrates)

   • Noncytoplasmic side only (= extracellular side = lumenal side)

   • Attached to membrane lipids and proteins in the ER and the Golgi (done by enzymes)

   • Functions: Protection, lubrication, adhesion (helping cells stick to things or other cells), communication, cellular migration, etc.

   • Ex: Lymphocyte

     • Has extremely large nuclei

Membrane Proteins

Membrane Domains

• Portion of an integral membrane protein that is actually embedded in the bilayer; consists of all or mostly hydrophobic amino acids

  • Ex: Single alpha helix

    • Monolayer - one half of bilayer

    • Transmembrane domain - span both halves of bilayer (~19 amino acids)

      • Hydrophobic side chain amino acids have to face outward

      • Includes many receptors, enzymes, and recognition proteins

        • Ex: mHCI - Major histocompatibility complex; almost no chance that 2 people have the same one

        • Ex: mHCII - Heterodimer (two different subunits/alpha and beta); disulfide bonds facing outward to help hold shape of molecules together

        • Ex: CD4 and CD8 - Co-receptor on T cells (CD4) and activated t-lymphocytes when you get an infection. CD8 is a heterodimer with disulfide bonds anchoring to the plasma membrane

        • Ex: Golgi sialyltransferase - Enzyme embedded in the Golgi membrane by way of an alpha helix that adds sugars to proteins in the Golgi

  • Multiple alpha helices

    • Includes many in ion channels, receptors, and membrane-embedded enzymes

    • Often ½ of each alpha helix is hydrophobic and ½ is hydrophilic

      • Ex: bacteriorhodopsin-7 transmembrane alpha helices

        • Light absorption + proton pumping (photosynthesis in Halobacteria, more specifically Halobacterium salinarum).

      • Ex: G-Protein-coupled Receptor

        • Large family of receptors for cytokines, hormones, neurotransmitters, pheromones, etc… all have 7 transmembrane alpha-helical domains

          • β-adrenergic receptor = epinephrine receptor = adrenaline receptors

        • Smell and taste receptors

        • Opsins + rhodopsins (vision)

          • Ex: Voltage-gated Na⁺ ion channel involved in action potential in neurons (24 transmembrane alpha helices)

• One or more “rolled sheets” (β-barrels)

  • Ex: Porin in outer membranes of gram-negative bacteria + outer membrane of mitochondria

Kyte-Doolittle Hydropathy Plot

• Method to identify membrane domains in membrane proteins; graph of amino acids at each position vs. hydropathy score

• Hydropathy Score:

  • More positive = more hydrophobic

  • More negative = more hydrophilic

• Each position represents an amino acid

• Each score above 0 is hydrophobic; each score less than 0 is hydrophilic

• LSS = Leader Sequence

Acetylcholine

• Four transmembrane alpha helices (M1, M2, M3, and M4)

• LSS is hydrophobic

Chapter 12: Membrane Transport

Intracellular vs. Extracellular Environment

Phospholipid bilayers are selectively permeable.

• Small, hydrophobic molecules are able to cross the membrane very quickly and easily

  • O₂, CO₂, N₂, benzene

  • Makes cell respiration easy as it does not have to have any specific dedicated carrier or transporter due to the concentration gradient created

• Small polar (partial charge) molecules are able to cross the membrane easily on their own, just takes a little more time to wedge through the phospholipids

  • H₂O, glycerol, ethanol

• Larger (3 carbons or more) polar molecules are not able to cross on their own because they are bulky and polar (hydrophilic)

  • Amino acids, glucose

• Ions + Charged molecules do not cross on their own

  • H⁺, Na⁺, HCO₃^-, K⁺, Ca²⁺, Cl^-, Mg²⁺, amino acids, nucleotides

Types of Membrane Transporters

1. Channel Protein - Creates a hydrophilic pore to allow ions to move in or out of the cell

   • Passive only → Facilitated diffusion (high to low concentration through the hole)

   • Selective based on size and charge

   • Constitutive (always open) and Gated (open or closed) channels

     • Voltage-gated ion channels (open/close based on charge/electrolyte balance or imbalance)

     • Ligand-gated

     • Mechanically-gated

   • Ex: K⁺ ion channels

     • Most common type

     • Present in most cell types

     • Many subtypes

       • K⁺ leak channels - Constitutive; help maintain resting membrane potential

       • Ca²⁺ Gated - Open only in response to high levels of [Ca²⁺]

       • Voltage-Gated K⁺ Channel - Open in response to changes in resting membrane potential

   • Ex: Voltage-Gated Na⁺ Channels

     • Help propagate action potential in neurons