Cell Surface Wk2 Flashcards
Give a basic overview of cell membranes
- Cells have a membrane to protect inside from outside
- Composed of lipids (mainly phospholipids) and proteins formed into bilayers
- There are two opposing sheets of lipids into which proteins are inserted
- Each lips has a hydrophobic tail and a hydrophilic head which defines the lipid bilayer structure
What features does the fluid mosaic model membrane have?
- Can deform membranes
- Proteins can move (dynamic structure)
- Can expand and contract
- Can break off and form other organelles
- Forms a barrier (lipid bilayer)
- Decides what goes in and out of the structure (protein molecule)
What is the organisation of lipids in phospholipid bilayer?
- Hydrophobic tails face each other (inner core of membrane)
- Hydrophilic heads face out towards fluids
- Fatty acid chains determine fluidity of membrane
- Charged so can interact with aqueous solutions
- Phospholipids are amphipathic (both philic and phobic)
What are the four major phospholipids in the mammalian plasma membrane?
- Phophatidylethanolamine
- Phosphatidylserine
- Phosphatidylcholine
- Sphingomyelin
What are intracellular signal transduction lipids?
- e.g. phosphatidylinositol, ceramide etc.
- Minor proportion of phospholipid content of intracellular membranes. Derived from lipids residing in the plasma membrane.
- Rapidly generated/destroyed by enzymes in response to a specific signal
- Spatially and temporally generated = highly specific signal
- Bind specifically to conserved regions found within many different proteins and once bound, induce confirmation and/or localisation and activity change within these proteins
What does cholesterol do?
- Inserts (intercalates) between membrane phospholipids
- This tightens packing in the bilayer/membrane rigidity (and density) and decreases membrane permeability to small molecules (goes against fluid mosaic model)
Why do biological membranes have to be fluid?
- Allow signalling lipids and membrane proteins to rapidly diffuse in the lateral plane and interact with one another e.g. in cell signalling (tyrosine kinase)
- Allows membrane to fuse with other membranes e.g. in exocytosis (transport vesicles)
- Ensures membranes are equally shared between daughter cells following cell division (membranes have to be fluid in order to split)
What are membrane protein functions?
- Transport
- Enzymatic activity
- Signal transduction
- Cell-cell recognition
- Intercellular joining
- Attachment to the cytoskeleton and extracellular matrix (ECM)
What are integral and peripheral membrane proteins?
- Single pass or multi-pass transmembrane proteins (integral)
- Peripheral membrane protein
- The transmembrane domains of integral membrane proteins are comprised of hydrophobic amino acids, which are organised into alpha-helical structures
What is a transporter?
Transport molecules across membrane - needed for polar/charged ions e.g. Na+ pump - move Na+ across the proteins
What are anchors?
Link structures to intracellular scaffolds (intern, actin)
What are receptors?
Bind ligands and/or generate a signal inside cell
What are signal transduction molecules?
Pass on and amplify signals (e.g. from outside cell)
What are two passive transport systems?
Simple diffusion:
- No membrane proteins involved
- Driven by concentration gradients
- Down a concentration gradient
- The ability of a solute to cross the membrane by simple diffusion depends on: concentration gradient, hydrophobicity/charge and size
- Membranes are highly impermeable to ions
Facilitated diffusion:
- Membrane proteins involved (have to help it move)
- Driven by concentration gradients
- Involves membrane proteins - 2 classes - Channels (discriminates mainly on size and charge) and uniporter carrier proteins (involves a binding site for solutes). They transport ions/small molecules across the membrane passively along their concentration/electrochemical gradients.
No energy input (ATP) required for either
What is a protein channel?
- Membrane proteins that form hydrophilic pores through the plasma membrane
- Most are non-directional ion channels (fundamentally a channel through the membrane)
- Shows some selectivity e.g. big pore = big ions
- Fast - up to 107 ions per second
- Gated channels offer more control than a simple membrane pore
What are uniporter carrier proteins/.
- Glucose transporter (Glut2) in gut epithelia
- Highly selective - transported molecule bound to carrier
- Relatively slow (<1000 molecules per second)
- Glucose passes from outside to inside via con transporter proteins
- Goes from outward facing state to inward facing state
What is an electrochemical gradient?
- Negative membrane inside, positive membrane inside - negative membrane means that +ve ions repulsed by positive membrane inside
- An electrochemical gradient (produced by a change in charge = ‘membrane potential’) combines the concentration gradient and membrane potential
- The force driving. charged solute (e.g. Na+ ions) across a membrane is the concentration gradient and the membrane potential
Why do cells maintain electrochemical gradients?
- To drive transport across membranes
- To maintain osmotic balance
- Electrical forces inside and outside of the cell must be balanced (most of the time) (though small localised differences at the plasma membrane are allowed)
- Without active transport to maintain electrochemical gradients, ions would flow down their gradients through channels, disturbing the osmotic balance
What is active transport?
- It moves solutes against their electrochemical gradients
- To achieve this movement against the electrochemical gradient, energy is required
What are ATP driven pumps?
- Moves solutes against the concentration/electrochemical gradient by expending energy (primary active transport)
- E.g. Na+ and K+ electrochemical gradient
- In the absence of Na+/K+ ATPase ions would flow down their gradients disturbing osmotic balance and preventing ‘secondary’ active transport
How is the Na+ electrochemical gradient maintained?
- Protein hydrolyses ATP and is phosphorylated. 3Na+ ions bind.
- Na+ dependent phosphorylation causes pump to undergo conformational change. 3Na+ pumped out.
- 2K+ pumped in and pump is dephosphorylated.
- K+ dependent dephospho rylation causes the pump to return to its original conformation. K+ is transferred across the membrane and released.
- 30% of cell’s total energy consumption is used in operating this pump
- Operated continuously to expel Na+ that enters cell through other carrier proteins and channels
- Hydrolyses ATP to ADP e.g. is both an enzyme and a carrier protein
- Couples the export of Na+ to the import of K+ hence the name
How do cells carry out active transport?
- ATP driven pumps - couple the transport of a solute against its gradient to the hydrolysis of ATP (all done on same protein) - primary active transport
- Coupled transporters - couple the transport of one solute with the gradient to another against the gradient - secondary active transport
What are coupled transporters?
- Move solutes against concentration/electrochemical gradient by coupling transport to Na+ gradient created by Na+/K+ ATPase.
- Do not depend directly on the hydrolysis of ATP (e.g. secondary active transport)
What is a symport?
- Na+/glucose symporter
- Both things move in together
What is an antiport?
- Na+/Ca2+ antiporter
- Work in opposite to each other
Explain the Na+/gluose symporter in gut epithelia
- Na+ electrochemical gradient used to drive the movement of glucose against its gradient
- Binding of Na+ and glucose is co-operative i.e. binding of glucose is dependent on Na+ because Na+ is much higher outside the cell glucose is more likely to bind facing extracellular space than intracellular space
- Protein wants both things to bind together - its doesn’t use ATP itself but Na+/K+ ATPase creates electrochemical gradient
- Overall result is that Na+ and glucose enter the cell more often than leave it - net flow is into the cell
What is the Na+/Ca2+ anti porter?
- Important in cardiac muscle: cardiac muscle cell contraction is triggered by a rise in intracellular Ca2+ - Ca2+ therefore reduced inside cell to not increase heart rate so much
- More Na+ outside than inside
- Energy of Na+ moving in down its electrochemical gradient forces Ca2+ outside
- The Na+/Ca2+ anti porter reduces intracellular (Ca2+) and thereby reduces strength of cardiac muscle contraction