Lecture 14: Movement Across Membranes

Morris: Chapter 5, section 5.2

Fluidity of biological membranes

Membrane fluidity must be maintained. Lipid composition of membranes can be changed by:

1. desaturation of fatty acid chains

2. exchange of fatty acid chains

Phospholipid organization

phospholipids spontaneously organize as stable structure in aqueous solution

Transmembrane proteins

transmembrane protein domain is a peptide sequence that is largely hydrophobic (uncharged) and spans across the plasma membrane

• alpha helix is the most common protein structure element

9 amino acids with hydrophobic side chains

glycine, alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan

Tetraspanins (TM4SFs)

super family of membrane proteins found in all multicellular eukaryotes

• four transmembrane alpha-helices

• two extracellular domains

  • one short (EC1)

  • one long (EC2)

• can be glycosylated (attachment of a carbohydrate molecule) on the long extracellular

• plays a role in: cell adhesion, motility, proliferation, etc

Movement across cell membrane

• lipid bilayer don’t allow many substances to pass through freely:

  • can: small, uncharged molecules cross membranes relatively easy (O2, CO2, NO)

  • can’t: large, polar, charged molecules (Ca+, Glucose, Na+, K+)

    • can transport with mechanisms/controlled transport

There are 4 basic mechanisms for moving molecules

Passive (1-3), Active (4)

1. simple diffusion

2. diffusion through a channel

3. facilitated diffusion

4. active transport

Crossing membrane: passive

relies on molecular concentration, small neutral molecules

Crossing membrane: simple diffusion

goes down a concentration gradient

Crossing membrane: channels

down concentration gradient, passive, small charged molecules

• uniporter only 1 molecule, i.e. sodium channel

• ion channel: gated open/close in response to different stimuli

  • ligand-gated channels

  • voltage-gated channel

What do voltage-gated channels do?

• voltage-gated channel: respond to charge changes across membrane; i.e. Na+ and K+

  • cell membrane potential: difference in charge across membrane

  • action potential: passage of electric signal down a nerve axon

What do ligand-gated channels do?

• ligand-gated channels: responds to binding of a specific molecule called a ligand; i.e. acetylcholine receptor

  • the binding produces a conformational change in the structure of the receptor/channel

Tetrodotoxin (TTX)

• potent neurotoxin

• discovered in oufferfish

• Na+ channel blocker → inhibits the firing of action potentials in neurons by binding to voltage-gated sodium channels in nerve membranes and blocking the passage of Na+ ions into the neuron

  • prevents nervous system from carrying out messaging

Curare

• mixture of organic compounds used as a paralyzing tool

• competitive antagonist of the nicotonic acetylcholine receptor (nAChR)

  • occupies the same position on the receptor as ACh and elicits no response, thus is an example of depolarizing muscle relaxant

Crossing membrane: carriers

• facilitated diffusion

• glucose transporter: import glucose down a concentration gradient

• symporter

Crossing membrane: carriers - facilitated diffusion

Substrate binds to integral membrane protein called a facilitative transporter, resulting in transporter conformation releasing the compound on other side moving down the concentration gradient

Crossing membrane: carriers - glucose transporter

import glucose from blood down concentration gradient using facilitator

Crossing membrane: carriers - symporter

not reliant on concentration gradient (low → high), relies on chemical gradient of another molecule that wouldn’t reach equilibrium

e.g. Na+ Glucose Symporter: outside, high Na+ low glucose, inside, low Na+ high glucose → 2Na + 1 glucose binds → conformational change (occluded conformation = closed both sides) → inward and releases the three → return to resting position/outward

Crossing membrane: carriers - antiporter

concentration gradient of one molecule is used to transfer second molecule in opposite directions

e.g. sodium-proton exchanger: transports Na+ into cell and protons out of cell

Crossing membrane: active transport

substrate binds to to integral protein/active transporter → hydrolysis of ATP causes conformation to release molecules onto other side of membrane

• Na+/K+ pump 3Na leaves and 2K enters and high Na+ concentration outside of cell

  • maintains cell size