Plasma membrane & Junctions Flashcards
3 main functions of plasma membrane
- substance import/export (acts as a selective barrier)
- compartmentalisation
- allows for movements (eg. pseudopods)
plasma membrane components
- phospholipid bilayer
- cholesterol
- proteins
- glycolipids/proteins
- cytoskeleton connections on intracellular compartment
structure of phospholipid
-phosphate polar head (hydrophilic): heads can either contain serine, inositol or choline alcohol residues which impact membrane fluidity and properties
-2 hydrocarbon lipid tails of different lengths and saturation that are non polar and hydrophobic
different families of phospholipids
- Phosphoglycerides: most abundant (in all cell membranes) and have glycerol backbone
- Sphingolipids have an apolar and polar side and their backbone is made of the amino-alcohol sphingosine
what arrangement do phospholipids take when exposed to water and why
Spontaneous closure into either a bilayer, lysosome or micelle. Aggregation to arrange hydrophobic tails internally and hydrophilic heads externally –> avoids exposure of lipid tails to water which is energetically favourable
thickness of plasma membrane and thickness of internal membrane (organelles)
plasma membrane: 7.5 nm
internal compartment membrane: 6nm
Evolution of theories regarding plasma membrane
- Charles Overton (1890s): stated that cells possess a lipid ‘coat’ on the outside
- Gorter-Grendel (1925): observed that phospholipids have a bilayer arrangement
- Davson-Danielli (1935): ‘sandwich model’ where proteins covered inner and outer environment (only surface, no integral proteins)
- Singer-Nicolson (1972): fluid mosaic model where proteins laterally move in bilayer and can be integral
Factors affecting the fluidity of plasma membrane (5)
- temperature (+)
- length of fatty acid tails (-)
- abundance of integral proteins (-)
- cholesterol (+/- depending on fatty acid tail chemistry)
- % of unsaturated fatty acid tails (kinks) (+)
How does the presence of cholesterol affect the plasma membrane
ROLE: interacts with fatty acid tails to influence fluidity (either positively or negatively)
- for SATURATED fatty acid tails (no double bonds): increase fluidity by preventing fatty acids from packing too close together.
- for UNSATURATED fatty acid tails (double bonds): decrease fluidity by filling in gaps in membrane caused by kinks, anchoring the tails.
How is movement of phospholipids within membrane enabled?
MOVEMENT VIA DIFFUSION:
-lateral drift in the plane of membrane
-RARE: switching of phospholipids between inner/outer leaflets due to flip/flopase enzyme activity (eg. important in apoptosis)
3 main properties of the plasma membrane
- fluidity (lateral movement of proteins and phospholipids is allowed)
- discontinuity (structure is interrupted by integral proteins)
- asymmetry (disequilibrium of inner and outer leaflet)
2 factors maintaining membrane asymmetry
- TRANSVERSE asymmetry: structural differences through thickness of membrane
- PC (choline phospholipids) mainly on outer leaflet
-PS (serine phospholipids) mainly inner leaflet
-Glycolipids exclusively on outer layer
-Carbs only attached to outer membrane proteins
-glycocalyx only on outer layer - REGIONAL asymmetry: specialisation of membrane at different sites (cell polarity) - eg, different morphologies of lateral/apical/basal cell surfaces
what is the freeze fracture technique?
-allows visualisation of plasma membrane by splitting it into 2 layers to observe proteins that are completely embedded
PROCESS:
-tissue is frozen and cut along the hydrophobic plane in the middle of the bilayer
-creation of E-face (backed by extracellular portion) and P-face (backed by cytoplasmic/protoplasm portion)
-TEM used to visualise each face
!!! usually P face contains more proteins/particles than E face
2 protein location types on plasma membrane
- integral proteins: found within bilayer
- extrinsic proteins: non covalently associated with either inner or outer leaflet of membrane
6 types of membrane proteins and basic functions
- pumps: active ion transport
- channels: passive diffusion along conc grad
- receptor proteins: localisation of ligands for cell signalling pathways
- linker proteins: anchor extracellular matrix with the intracellular cytoskeleton
- enzymes: ATPase and digestive enzymes
- structural proteins: form junctions with surrounding cells
Lipid raft definition
Microdomains of the plasma membrane which are dynamic (control movement and distribution of proteins in bilayer), and enriched with sterol and sphingolipid domains.
Due to presence of cholesterol/highly saturated fatty acid tails these regions show less fluidity and are thicker
function of lipid rafts
mainly caveolin and flotillin proteins: recruit signalling molecules so that they serve as centers for assembly of signalling receptors (GPCRs, RTKs)
2 types of lipid rafts
- Planar lipid rafts: found in neurons, run in line with the plane of the membrane and are enriched in the protein flotillin (scaffolding protein)
- Caveolae: flask shaped invaginations of membrane containing caveolin proteins (prominent in smooth muscle cells)
Relevance of lipid rafts in infection
Lipid rafts are often the location of initial contact between microorganism and cell:
-bacteria hijack rafts and attach their own receptors
-use of rafts to avoid phagocytosis or degradation via lysosome
-use of raft receptors to create vehicles transporting bacteria into cell without their breakdown
Glycocalyx structure and function
-STRUCTURE: carbohydrate coat (containing some proteins) covering outer leaflet (not present on inner membrane)
-FUNCTION: filtering material, regulating close cell interactions, involved in cell adhesion mechanism, contains enzymes and antigens
Types of transport across membrane
Membrane possesses selective permeability depending on type of substance:
- SIMPLE DIFFUSION: small/non polar molecules
- FACILITATED DIFFUSION: small polar molecules either via carrier or channel proteins
- ACTIVE TRANSPORT: ions and larger charged molecules via pumps (active carrier proteins) using ENERGY
- BULK TRANSPORT: transport of hormones/ steroids via vesicular transfer: endocytosis and exocytosis using ENERGY
components and function of endomembrane system
CONTAINS: RER/SER/lysosomes and vesicles /nuclear envelope/Golgi apparatus
FUNCTION: system of lipoprotein membranes that form intracellular packaging and transport network
Types of junctions (5)
OCCLUDING: tight
ANCHORING: adherens, desmosome, hemidesmosome
COMMUNICATING: gap
structure and function of tight junctions
-point to point fusion of adjacent cells for localised sealing
1. acts as a diffusional blocker: materials can’t pass from lumen to extracellular space
2. maintains cell polarity: blocks movement of apical specific structures so that they are not lost to the lateral surface
STRUCTURE:
-claudin, occludins and tricellulin proteins joining in intercellular space
- connection to zona occludins attached to actin filaments on the intracellular portion of membranes
-intracellular connection to ZO1/2/3 (Zonula Occludens 1/2/3)
-connection to JAM (junction adhesion molecules) acting as signalling molecules
!!! found in blood-brain barrier and GI tract, Sertoli cells for blood-tests barrier in seminiferous tubule
structure and function of adherens junctions
-provide adhesion between adjacent cells to provide resistance to shearing/abrasive forces
STRUCTURE:
-E cadherins joined with Ca2+ in intercellular space
-connection to beta and alpha catenins on plasma membrane
-connection to vinculin proteins that join to actin filaments
!! Found mainly on the same tissues as tight junctions (but are found slightly more basally)
pathology resulting from malfunctioning adherens junctions
carcinomas occur with the down regulation of e-cadherins
structure and function of desmosomes
-similar to adherens junctions but STRONGER resistance to shearing forces, and tensile strength is provided
STRUCTURE:
-interlocking cadherin proteins in intercellular space
2 types: desmoglein (1-4) and desmocollin (1-3)
-Ca2+ keeping proteins interlocking
-connection to plaque proteins (desmoplakin and plakoglobins) which link to intermediate filaments containing keratin
!!! prominent in cardiac myocytes (intercalated discs), oral mucosa layer
structure and function of hemidesmosomes
-connect cell membrane to basal lamina (form basement membrane)
STRUCTURE:
-integrin proteins connecting cell and lamina
-connect to desmoplakin proteins
-link to intercellular intermediate filaments like keratin
!! prominent in the skin/epithelial tissue
structure and function of gap junctions
-used for cell to cell communication by allowing passage of ions/small molecules through adjacent cells
-this is important in homeostatic control of cell proliferation: apoptosis
STRUCTURE:
-made of 2 connexons linked together between membranes
-each made up of 6 connexins
!! prominent in cardiomyocytes (intercalated discs), electrical synapses of neurons, epithelial cells
Pathologies arising from malfunctioning gap junctions
Connexins: tumour suppressors
transformed cancer cells usually show mutations in connexins/connexons which breaks gap junctions and affects communication between cells
-throws cell proliferation: apoptotic ratio in disequilibrium –> tumorous growth
How are channels of gap junctions regulated
certain substances induce opening or closing od channels:
- Ca2+ binding opens channels
- phosphorylation of connexins (closed when phosphorylated)
Types of active transport
- symport systems: two substances moved across a membrane in the same direction
- antiport systems: two substances are moved across a membrane in opposite directions
!! all need ATP
primary vs secondary active transport definition
PRIMARY: uses energy in the form of ATPdirectly to move solutes against conc gradient
SECONDARY (cotransport): does NOT utilize ATP directly. Instead, it uses one ion going down its concentration gradient to drive the movement of another ion going against its concentration gradient.
