1-14 Membranes and Microscopy Flashcards
What are the five major functions of biological membranes, and why are they important?
- Selective permeability: control what enters and exits cells/organelles
- Compartmentalization: organelles can have wildly different chemical environments and functions
- Identification: unique identity of cells/organelles based on membrane units/conents
- Signaling: transmembrane signaling transduction acts as “sentry system”; learn about external environments without having to expose the cell to them
- Energy storage: membrane gradients can act to store energy
Disruption of function can lead to disease.
What are the common features of biological membranes?
- Composition: lipids, proteins, carbohydrates
- Structure: asymmetric, sheet-like bilayers that can form closed compartments
- Held together by noncovalent interactions
- Fluid under physiological conditions
- Relatively impermeable to polar, hydrophilic molecules
- Most specific functions carried out by membrane proteins
What are the primary properties of lipids in biological membranes?
- Amphipathic
- Mostly phospholipids: polar head group + backbone + nonpolar hydrocarbon tail
What are the hydrophobic and hydrophilic parts of phosphoglycerides?
Hydrophobic: fatty acid chain
Hydrophilic: phosphorylated alcohol
What are the hydrophobic and hydrophilic parts of sphingomyelin?
Hydrophobic: fatty acid chain and hydrocarbon chain of sphingosine
Hydrophilic: phosphoryl choline
What are the hydrophobic and hydrophilic parts of glycolipids?
Hydrophobic: fatty acid chain and hydrocarbon chain of sphingosine
Hydrophilic: One or more sugars
What are the hydrophobic and hydrophilic parts of cholesterol?
Hydrophobic: everything except -OH
Hydrophilic: -OH group
How do membrane lipids act in aqueous solution?
They will aggregate and bury their hydrophobic tails while exposing their hydrophilic heads. They can form either spherical micelles or bilayers.
Due to the prevalence of phospholipids, most membrane lipids will preferentially form bilayers.
What is the most energetically favorable shape for lipid bilayers in aqueous solution, and why?
Lipid bilayers will spontaneously close on themselves to form closed vesicles, thereby shielding hydrophobic regions and exposing hydrophilic regions as much as possible.
This phenomenon is primarily driven by the hydrophobic effect, but it’s also supported by van der Waals forces (close packing of hydrocarbon tails) and interactions between polar head groups and water (electrostatic and H bonding).
What are the typical movements of bilayer lipids?
- Lateral diffusion
- Flexion
- Rotation
RARELY, lipids will flipflop between layers. This is typically mediated by proteins.
What factors influence the fluidity of membranes?
- Temperature: at physiological temp., membranes are disordered and fluid. Below phys. temp., they are ordered and gel-like.
- Length and degree of saturation: long, saturated HC chains interact more strongly due to van der Waals interactions. In unsaturated chains, double bonds produce kinks that prevent tight packing and allow for more fluidity.
- Cholesterol content: tends to decrease fluidity because it blocks large motions of saturated HC chains; however, it also can prevent membranes from solidifying to gel phase because it prevents nearby fatty acyl chains from packing too tightly.
What are lipid rafts?
Membrane subdomains that tend to be thicker, be less fluid, and contain higher content of sphingolipids (sphingomyelin and glycolipids), cholesterol, and some proteins. They float within the bilayer and are thought to help aggregate membrane proteins for transport and/or assembly.
Why are lipid bilayers asymmetric?
Outer half: mostly phosphotidylcholine, sphingomyelin, glycolipids
Inner half: mostly phosphotidylserine and phophotidylethanolamine
(cholesterol is distributed evenly)
The asymmetry is important for cell signaling across the membrane and identification of live/dead cells.
ex) Phosphatidylserine moves inner half –> outer half during apoptosis, signaling for phagocytosis.
What determines a molecule’s ability to pass through a lipid bilayer?
- Polarity: nonpolar molecules can cross easily; polar molecules cannot
- Size: small molecules will cross more easily than large ones
Aquaporins will allow water molecules to pass more easily.
How do drugs get into cells, and what are the drawbacks?
- Passive diffusion: drug is hydrophobic enough to pass through the bilayer but hydrophilic enough for easy distribution. Cons: structurally limiting
- Hijacked transporters: drug looks like some other molecule that is normally transported by membrane transport proteins. Cons: structually limiting (but manipulatable)
- Liposome delivery: drug is packaged in liposomes and targets cells with a membrane protein tag. Cons: difficult to control, inefficient, liposome contents not always released easily
- Protein transduction: drug is coupled to and taken up by protein sequences that interact directly with the bilayer. Cons: new, not used therapeutically
How can the lateral diffusion of membrane proteins be constrained?
- *A)** Anchoring the protein to an intracellular structure, like the cytoskeleton
- *B)** Anchoring the protein to an extracellular structure, like the ECM
- *C)** Protein-protein interactions between cells, like neurological synapses
- *D)** Barriers established by junction proteins
