5: Membranes Flashcards
Describe the major components of membranes and how they are organised.
Phospholipid bilayer
Cholesterol to stabilise membrane by maintaining its fluidity
Intrinsic proteins span the membrane, often serving as channels, transporters, or receptors
Extrinsic proteins often involved in signalling, enzyme activity, etc.
Glycolipids or glycoproteins involved in cell recognition and signalling
Fluid mosaic model
Membrane often organised into domains/regions with specific functions (e.g. lipid rafts)
What is a lipid raft?
A specialised micro-domain within the plasma membrane that is enriched in certain lipids such as cholesterol
Formed by caveolin coat proteins
Regulates cellular signallling pathways
What are micelles?
Spherical structures formed by the self-assembly of amphipathic molecules in an aqueous environment
Hydrophilic heads of the amphipathic molecule face outwards
Hydrophobic tails face inwards away from water
Important in solubilisation of hydrophobic molecules such as oils and lipids
What are liposomes?
Spherical vesicles composed of one or more lipid bilayers
Encapsulates aqueous solutions
Formed when phospholipids or other amphipathic lipids are exposed to water
Causing a self-assembled bilayer
Often used in targeted delivery of molecules like ligands or antibodies
Compare micelles and liposomes.
Micelles:
Amphipathic
Monolayer
Hydrophobic core
Encapsulates hydrophobic substances
Small
Liposomes:
Spherical vesicle with one or more phoshpolipid bilayers
Bilayer
Aqueous core surrounded by bilayer
Larger
What are detergents?
Amphipathic molecules (have both hydrophobic and hydrophilic regions)
Interact with bilayers to disrupt, solubilise or modify membranes
Used widely in cell biology and biochemistry to study membranes and protein structure
E.g. Triton X-100, SDS
Describe the freeze-fracture electron microscopy experiment.
Rapidly freeze a biological sample to immobilise structures
Fracture the sample using a cold knife in a vacuum, this splits it along the hydrophobic core of the lipid bilayer because this is the weakest part of the membrane
Produces two faces
Fractured surfaces coated with a thin layer of metal like platinum to create a shadow effect, followed by a stabilising layer of carbon
The original bioloigcal material is dissolved away, leaving a metal replica
The replica is examined using TEM
Shows that proteins aren’t evenly distributed across both layers, confirming the fluid mosaic model
Compare selective and non-selective uptake through membranes.
Selective uptake is controlled, specific, and often involves protein-mediated transport
Can be active or passive
Non-selective uptake is less specific, often passive, and may occur via bulk flow or endocytosis
Often by processes like simple diffusion
Compare active and passive transport.
Passive:
Requires no energy, high to low conc, sometimes involves carriers/channels, generally fast, selectivity varies, results in equilibrium
Active:
Requires energy, low to high conc, always involves pumps/cotransporters, slower due to energy and conformational changes, very high selectivity due to specific transporters
How are transporters organised in a polarised epithelial cell?
On the apical membrane (facing the lumen): transporters typically function to uptake nutrients, ions, water, etc.
On the basolateral membrane (facing the bloodstream): transporters typically export absorbed substances into the interstitial fluid/blood and maintain electrochemical gradients
This is important as it maintains efficient nutrient uptake and waste removal and prevents backflow
What are some mechanisms of taking up large molecules?
Phagocytosis
Pinocytosis
Receptor-mediated endocytosis
Summarise phagocytosis.
Highly specific
Takes up large particles like microbes
E.g. macrophages ingesting bacteria
Phagosomes then fuse with a lysosome for digestion
Summarise pinocytosis.
Non-specific
Takes in soluble material
Continuous, non-selective process in many cell types
Carried out by Clathrin coated vesicles
Summarise receptor-mediated endocytosis.
Very highly specific
Target molecules bind to specific receptors
Receptors cluster in regions rich in clathrin adaptor proteins
Adaptor proteins recruit clathrin to the cytoplasmic side of the membrane
Clathrin triskelions polymerise into a curved lattice, forming a coated pit
Clathrin-coated pit deepens and buds inwards from the membrane into the cell
Dynamin, A GTPase, pinches off the vesicle
What is Clathrin?
A key coat protein involved in receptor-mediated endocytosis and pinocytosis
Describe uptake of LDL by receptor mediated endocytosis.
1) LDL binds to LDL receptor (LDLRs) on the plasma membrane
2) Clathrin-mediated endocytosis internalises the LDL-LDLR complex into a clathrin-coated vesicle
Vesicle uncoats and fuses with an early endosome
Acidification in the endosome causes LDL dissociation from LDLR
LDL is processed in the lysosome
LDLR recycled back to plasma membrane
Classify intracellular signalling in both spatial and functional terms.
Spatial classification focuses on where the signals are coming from and where they go within the cell
Functional classification categorises the purpose and effect of the signalling pathways, such as regulating metabolism, gene expression, or cell growth
What is intracellular signalling?
The complex network of molecular signals and mechanisms that allow cells to communicate and co-ordinate responses to various internal and external cues
Signalling regulates a wide range of cellular functions including growth, metabolism, differentiation, and response to environmental stimuli
How do macrophages remove cells after apoptosis?
Macrophages extend pseudopodia
These then surround and engulf the target
Once engulfed the cell forms a phagosome
Phagosome fuses to a lysosome and contents are digested
What are macrophages?
Type of white blood cell
Engulfs microbes
Use pseudopodia to extend and identify targets before endocytosing them
What are the three possible fates of endocytosed receptors?
1) Recycled into the membrane
2) Degraded in lysosomes
3) Transcytosed to the other end of the cell
Describe transcytosis in epithelial cells.
E.g. milk
Antibodies from milk bind to receptors on apical surface
They are then internalised and delivered to endosomes
Retrieved from transport vesicles which bud off from early endosome
Fuse with basolateral domain of plasma membrane
What is an endosome?
A type of transport vesicle that carries soluble proteinsaround the cell
What are the three types of coated vesicle?
1) Clathrin coated (e.g. endocytosis using RME)
2) Non-Clathrin coated (mediates vesicular transport)
3) Caveolar vesicles