Lecture 16. Cell motility and chemotaxis

Question 1

How does a cell sense and respond to its extracellular environment while maintaining internal compartmentalization?

Answer 1

• Cell needs to be able to sense the EC environment in a conc dependent manner
  
  • Chemotactic: signaling pathways that can alter the cytoskeleton to allow the cell to change shape n move towards the direction of the signal
    ○ Can move towards (positive) or away (negative) from the signal
    There must be coordination of the internal so that compartmentalization of the cell can be maintained as the cell moves towards that particular direction

Question 2

Describe how Dictyostellium discoideum aggregates in response to cAMP

Answer 2

• Slime mould that lives in a single cell state when it is fed
  
  • When food becomes limiting, cells send out a signal to each other (EC cAMP)
    ○ Tells cells to group together at the cAMP source n join together to form a motile slug
  • Becomes a fruiting body
    Can live for a long time w/o any nutrients

Question 3

What is chemotaxis?

Answer 3

Ability to sense and move towards or away from a directional signal.

Question 4

Design an experiment where you can observe Dictyostellium Discoideum moving towards a source of cAMP

Answer 4

• If an artificial cAMP source is given to these cells, they will aggregate towards it
• Cells will all move towards the pipette tip
• Each of those cells snse the highest conc of cAMP n changing direction rapidly in order to move
  This basic movement is conserved in other organisms

Question 5

What is chemotaxis important for?

Answer 5

• Directed cell movements during development (e.g. gastrulation, neural crest migration n primordial germ cell migration)
• Immune surveillance (phagocytosis of pathogens)
• Inflammatory response to injury (lymphocyte migration) n wound healing (fibroblast migration)

Question 6

How do neutrophils respond to fMet-Leu-Phe secreted by bacteria?

Answer 6

• Bacteria secretes a tri-peptide called fMet-Leu-Phe (fMLP) which is sensed by receptors on the neutrophil plasmamembrane.
• The non-motile cells are red blood cells. Note that the neutrophil “walks” on the underlying glass slide to move itself forward.

Question 7

How is the zebrafish larva used as a model organism in studying inflammatory responses and wound healing processes?

Answer 7

• Zebrafish larva is opaque thus good for microscopy
  
  • To mimic wounding, the fin of an anesthetized larva is pierced w a needle
  • This stimulates a rapid inflammatory response
  • Lymphocytes can be seen migrating to the site of injury
  • Fibroblasts which initially appear static will migrate to the wound site to repair the wounded area
  • Attracted by chemicals released by the wound
  • Lymphocyte is restricted to the wounded area

Question 8

Describe the process of cell locomotion

Answer 8

• Locomotion begins w the extension of 1 or more lamellipodia from the leading edge of the cell
  ○ Involves branched actin polymerization which pushes the membrane forward
  
  • New focal adhesions (feet) Are formed at specialized sites on the plasma membrane
    ○ Contain integrins which link actin to the ECM
  • Translocate: bulk of cytoplasm is pushed forward by contraction of actin-myosin II bundles (stress fibers) at the rear of the cell
  • Endocytic recycling: trailing edge of the cell detaches from the ECM n retracts into the cell body
    During this process, the endocytic machinery internalizes integrins n transports them to the front of the cell to be used again