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what’s the structure of a phospholipid?
A glycerol backbone + 2 long chain fatty acids (14-24 atoms of carbon) and a phosphorylated head group.
Why do phospholipids spontaneously form a lipid bilayer in water? What happens when they do this?
To minimize free energy. The hydrophobic tails cluster inward an the hydrophobic heads face the aqueous environment.
What happens if the lipid bilayer is torn?
It spontaneously reseals. Exposure of hydrophobic tails to water is energetically unfavorable.
Why is the continuous nature of plasma membranes maintained?
No free edges! This is to avoid exposing hydrophobic regions to water.
What is the most abundant phospholipid in animal and plant membranes?
phosphoatidylcholine. This has the small molecule choline attached to a phosphate group as its hydrophilic head.
What are liposomes?
These are pure phospholipids that can form synthetic bilayers called liposomes to study lipid movement.
When a hydrophobic molecule is placed in water, what does it force the water to do?
Form a cage-like structure around it. Hydrophobic molecules form fat droplets.
What happens if a tear in the plasma membrane is large?
it might begin to fold in on itself and separate into closed vesicles
What are the types of movement in the bilayers?
There’s
lateral diffusion: where lipids move sideways in the same leaflet
flexion: where their hydrocarbon tails flex and bend
rotation: where they spin around rapidly
transverse flip-flop: where phospholipids switch to the other side of the leaflet without protein assistance. This is very rare because it costs a lot of energy.
What does the fluidity of the lipid bilayer depend on?
Composition!
What are the two major properties of hydrocarbon tails that affect how tightly they pack together?
Their length and their number of double bonds.
Shorter chain length reduces the tails' tendency to interact. Fluidity increases.
Double bonds create kinks in the tail, making it harder to compact → fluidity increases.
In animal cells, membrane fluidity is modulated by the inclusion of what?
Sterol cholesterol. This molecule is present in large amounts, constituting about 20% of the lipids in the membrane by weight.
Cholesterol can fill the spaces between the neighboring phospholipid molecules left by the kinks. Cholesterol can stiffen the bilayer (less flexible, less permeable)
How does temperature affect membrane fluidity?
High temperatures: cholesterol decreases fluidity → movement is restricted
Low temperatures: cholesterol increases fluidity → tight packing of the Wmembrane is prevented.
Where are new phospholipids assembled?
The endoplasmic reticulum. They are made by enzymes bound to the cytosolic surface of the ER. They deposit new phospholipids only in the cytosolic half of the bilayer.
what do the enzymes making phospholipids use as subtrates?
free fatty acids!
What does scramblase do?
This is a transporter protein that removes selected phospholipids from one half of the bilayer and puts them in the other. This redistributes the phospholipids equally between each monolayer of the ER membrane.
Is the cell membrane symmetric or asymetric?
Asymmetric. Each side contains different sets of phospholipids.
Where does the asymmetry arise in membranes?
This happens at the Golgi apparatus. The Golgi membrane contains a transporter called a flippase, which is an energy-dependent action that moves phospholipids from one half of the bilayer to the other.
Why is the asymmetry of membranes important?
The asymmetry is characteristic of animal cells and helps them function.
It’s important that bilayers have a distinct inside and outside.
The cytosolic monolayer is enriched with what?
phosphatidylserine
phosphoatidylethanolamine
Phosphatidylinositols (used for cell signaling)
The non-cytosolic monolayer is enriched by what?
Phosphatidylcholine and sphingomyelin.
Glycolipids are exclusively found here. sugar groups face extracellular space.
What are glycolipids?
These are membrane lipids that face the exterior.
They form a coat of carbs that surrounds and protects animal cells.
They get their sugar groups in the golgi apparatus.
What are most of the membrane functions carried out by?
Membrane proteins! Which make up about 50% of membrane mass.
Name the ways in which membranes proteins can associate with the lipid bilayer.
Transmembrane: These are membrane that extend through the bilayer, with part of their mass on either side. These are amphipathic. Their hydrophobic and hydrophilic sides lie accordingly.
Monolayer-associated, anchored to the cytosolic layer by an amphipathic alpha helix
Lipid-linked: attached to a covalently bonded lipid
Protein attached: weak noncovalent links with other membrane proteins.
How do polypeptide chains usually cross the lipid bilayer?
As alpha helices.
Describe the structure of a alpha helix
Hydrophobic side chains - face outwards and interact with the trails of the phospholipids
Hydrophilic backbone - face inward, form h-bonds with itself internally.
What are single-pass proteins vs multi-pass proteins?
Single pass proteins pass through the cell membrane once, but multi-pass proteins sort of loop around and do it again.
Single-pass can function as a receptor, cell-adhesion protein, or signaling protein.
Multipass protein: commonly function as a channel, transporter, or receptor.
Multiple amphipathic a helices can make up what?
A transmembrane hydrophilic pore.
Example: five transmembrane alpha-helices can form a channel across the lipid bilayer. The hydrophobic side chains are on the outside of the pore, the hydrophilic side chains are on the inner side, forming a water-filled pore.
What’s the other form transmembrane proteins can take?
A beta sheet that is rolled into a cylinder, forming a keg-like barrel! this isn’t as common.
Amino acid side chains that face the inside.
Outside barrel- hydrophobic
Example is found in porin proteins.
How can you separate cell proteins from the membrane?
With detergents!
There are strong ionic detergents that denature proteins and fully disrupt the membrane. Ex SDS
There are mild nonionic detergents that solubilize the membrane while maintaining protein structure and function.
The solubilized proteins can be purified and then reconstituted into artificial phospholipid bilayers to study their behavior in isolation.
Where does our evidence for membrane proteins come from?
it comes from Freeze- Fracture Electron Microscopy
This is where the sample is frozen and fractured, which splits the bilayer into two faces, P and E.
The protoplasmic is adjacent to the cytosol and the extracellular is adjacent to the extracellular space.
Transmembrane proteins often stick with the p face and appear as bumps.
electron micrograph shows the lipid bilayer as a white thin layer with dark lines indicating the proteins in the bilayer.
Membrane proteins: What do transporters do?
Actively move specific ions or molecules across the membrane.
Membrane proteins: what do ion channels do?
allow specific ions to pass through passively
Membrane proteins: what do receptors do?
Bind extracellular signals and transmit information into the cell.
Membrane proteins: what do enzymes do?
Catalyze specific reactions within or on the membrane.
Membrane proteins: what does cell-cell recognition do?
Serve as identification tags for other cells.
Membrane proteins: what does intercellular joining do?
Form junctions between adjacent cells (tight junctions, gap junctions)
Membrane proteins: what does the attachment to cytoskelton/ecm do?
The extracellular matrix maintains cell shape and stabilizes protein location.
What is the cell cortex?
a network of fibrous proteins under the plasma membrane which enforce the membrane and restrict protein movement.
What are protein islands?
Plasma membrane associated proteins are clustered into islands attached to the cytoskeleton. Instead of being distributed evenly across the membrane, they cluster together.
how can cells restrict the movement of their membrane proteins?
Tethering to the cell cortex
Tethering to the extracellular matrix
Tethering to the proteins on the surface of another cell
Creating diffusion barriers that partition proteins to specific membrane domains.
What is FRAP?
This is fluorescence recovery after photobleaching.
It tags components with some sort of fluorescent marker
A small area of the membrane is irreversibly bleached with a laser
The recovery of fluorescence in the bleached area is monitored as unbleached fluorescent molecules diffuse in.
The rate of recovery directly measures the lateral diffusion rate of the protein.
What is SPT microscopy?
Single particle tracking.
Individual or small clusters of molecules are tagged
their movement is tracked over time
this can reveal different diffusion patterns (freely, diffuse, coralled)
What is SUPER-RESOLUTION MICROSCOPY
this is stuff like PALM dSTORM, and nanoimager
this overcomes the diffraction limit of light
allows visualization of fine morphological details and precise localization of individual molecules or vesicles
can track single vesicles and characterize multiple biomolecules simulataneously.
Where is the glycocalyx?
This is a carb rich layer on the outer surface of the plasma membrane
What’s the glycocalyx made up of?
Glycoproteins, proteoglycans, and glycolipids
What’s the function of the glycoalyx?
Cell-Cell Recognition: Essential for cell identification and communication.
Protection: Mechanical and chemical protection from damage.
Adhesion: Involved in cell-cell and cell-ECM adhesion.
Migration: Plays a role in processes like white blood cell (neutrophil) migration to infection sites, where lectins (transmembrane proteins) on endothelial cells bind to carbohydrate groups on the neutrophil glycocalyx.