Lecture 13: Membranes and Transport
Biological Membranes
◆ Complex lipid-based structures that form pliable (flexible) sheets
◆ Composed of a variety of lipids and proteins
◆ All cells have a cell membrane separating the cell from its surroundings
◆ Eukaryotic cells have internal membranes that divide the inside of the cell into subcellular compartments
◆ Membranes exist to segregate molecules
o Proteins that selectively move molecules across this barrier allow selective permeability that
can be controlled by the cell to
▪ Retain nutrients
▪ Expel toxins
▪ Generate chemical gradients (ex. proton gradient)
o Proteins also allow the cell to detect molecules on the exterior of the cell without letting them
inside : signal transduction
Fluid Mosaic Model
◆ Lipids form a 2D viscous fluid bilayer in which proteins are attached
o Some are deeply inserted with either hydrophobic regions of the protein or with hydrophobic
post-translational modifications that attach the protein to a lipid-like molecule
o Some are loosely associated, attaching and releasing
Common Features of Membranes
◆ ~ 3-10 nm thick
◆ Composed of two leaflets of lipids
***Exception: some achaebacteria are made of monolayer of bifuntional lipids
◆ Form spontaneously in solution due to the hydrophobic effect
◆ Need for complex curvature demands that membranes are asymmetric
o Inner leaflet usually has different lipid composition than the outer leaflet
o Certain subregions are enriched for certain lipids
, ***Example -- lipid rafts: regions of high cholesterol and glycosphingolipid content; important
functions in protein localization and signal transduction
o Carbohydrate moieties are usually outside the cell
o Electrically polarized
o Inside the cell is negative due to ion imbalance; ~60mV
◆ Membrane is fluid: 2D solution of lipids that flows and diffuses
o Fluidity influenced by lipid composition (unsaturated lipids, cholesterol, etc.)
Lipid Composition
◆ Varies in different molecules
o Different organelles, tissues, organisms
◆ Ratio of lipid to protein varies
◆ Type of phospholipid varies
◆ Abundance and type of sterol varies
o Cholesterol prominent in plasma membrane; almost completely absent in mitochondrial
membranes
Mammalian Membrane Composition Asymmetry
o Asymmetry required for
o Curvature
o Charge
▪ Interior more negatively charged; exterior more positively charged
o Signaling
▪ Phosphatidylserine (PS) on the outer leaflet of the plasma membrane marks most cells as
apoptotic, sends “eat me” signal to macrophages
▪ When platelets reach site of injury, PS is moved to out leaflet where it activates
coagulation
▪ How is PS moved?
Transverse Diffusion
o Spontaneous movement of an inner leaflet lipid to the outer leaflet is very slow (t1/2 is measured in days)
o Enzymes catalyze movement of lipids across leaflets
o PS maintained on inner leaflet in healthy cells by flippase; costs ATP because you are moving PS against
equilibrium
o Lipid equilibrium is restored by scramblases: don’t require ATP because they let the lipids equilibrate
between bilayers
, Function of Proteins in Membrane
◆ Transmembrane proteins MAJOR target for drugs; drug can act without entering the cell
◆ Receptors: detect signal from outside, and transmit signal to inside without moving signaling molecule
inside cell
o Light (opsin)
o Hormones (insulin receptors)
o Neurotransmitters
o Pheromones
◆ Channels, gates, pumps, and transporters
o Moves molecules from one side of the membrane to another
o Different categories based on type of molecule moved, mechanism of movement
◆ Enzymes; enzymatic activity often linked to another membrane protein activity (receptor, transporter)
o ATP synthesis (enzyme and proton channel)
o Lipid biosynthesis
Three Categories of Membrane Association
◆ Integral membrane protein: protein permanently mounted in membrane
o Transmembrane protein: protein passes completely through bilayer
▪ Binds a ligand on one side of the membrane, then undergoes a conformational change
that exposed the ligand to the other side of the protein, where it can be released
o Integral monotopic protein: protein imbeds into the membrane, but does not pass through
o Anchored protein: protein is anchored through lipophilic posttranslational modification
◆ Peripheral protein: usually bound to membrane by phospholipid head; dissociated with salt, pH, or when
denatured
◆ Amphitrophic protein: protein that moves to and from the membrane as part of its norm biological
activity