December 3: Questions about contact inhibition for class discussion and final exam questions! a) Can we be sure that Abercrombie's three statistical measures of contact inhibition, i.e.
2) few than twice as many "between" cells as "side" cells,
3) fewer overlaps between nuclei than would occur randomly
b) Try to imagine some behavior that would give a positive measure of contact inhibition by one or two of these three criteria, but not give a positive measure based on one or more of the other statistical criteria.
c) Li and Wang refer to contact inhibition as a "repulsive" phenomenon. Do you agree?
d) Would negative chemotaxis between cells be detected as if it were "Contact Inhibition,"based on some or all of these three statistical measures of contact inhibition?
e) Would the answer to this question differ depending on whether the negative chemotaxis acts only at short range, or whether chemotaxis acts at longer range?
f) Please invent statistical criteria for detecting and measuring "Contact Following".
g) Suppose there were an actual repulsive force that pushed cells away from each other, in that case which of the three statistical criteria of contact inhibition would measure this repulsion as being contact inhibition? (or indistinguishable from contact inhibition.)
h) Imagine that cell-cell contact caused both cells to stop, and remain stopped: Which of the three statistical measures would give an apparent positive measure of contact inhibition? And which would give a negative result? Could the result of #3 depend on whether cells stop immediately after cell-cell contact, as opposed to the result (i.e. reduction of nuclear over-laps) if contacted cells continued to move for a distance of about half the width of a cell, and then stopped completely? (Hint, which behavior would produce more overlaps between nuclei? )
i) Please invent statistical criteria able to detect contact inhibition among cells whose locomotion is channeled along straight grooves.
j) What about if locomotion is restricted to a grid pattern of perpendicular grooves?
k) Should it matter, in the sense of the three statistical measures of contact inhibition, whether cells consistently reverse direction after contact? Would a 180 degree reversal of direction produce a qualitatively distinguishable difference from the result of a 90 degree change in direction?
l) Li and Wang mention the idea of contact inhibition serving normal functions. Wound healing is the most obvious of such possible functions. (Would you agree or not? Explain.)
m) What about prevention of metastasis by cancerous cells as a likely function of contact guidance?
n) What about possible normal functions of contact following? Could gastrulation be such a function? Can you suggest any others? Can you suggest experiments or statistical tests of the idea that gastrulation is guided by contact?