What questions are being asked about cell sorting: Count how many?1) Is cell sorting caused by different adhesion proteins? Or by different amounts of some one adhesion model?
2) When does thermodynamics apply to cell behavior? (And when does it not?)
3) Are gastrulation and neurulation caused by the same mechanism as sorting out?
4) Is sorting out caused by the same mechanism as engulfment?
5) Did Phillips, Steinberg, Foty measure cell-cell adhesiveness, or were they actually measuring cortical contractility?
6) If cells converge on the same end result, by two or more different pathways, does that mean the phenomenon should be analyzed by thermodynamics?
7) Does the reversible work of adhesion necessarily exist? (if adhesion isn't reversible)
8) Are adhesion and attraction the same as each other? (DAH assumes yes)
9) Are theories useful? In what ways? (Can you design experiments without theory to test?
10) Is it proper for theoretical papers to be published by someone who has not published experimental results in a given particular field? (Herb Phillips regarded me as trespassing on his subject.)
11) Are moving cells pulled by maximization of adhesion, or by actomyosin contraction?
12) Gershman, Drumm and Culp (JCB 1976) discovered that cancer cells sort out external to equivalent normal cells; does that mean cancer cells are less adhesive, less contractile, or both? (As compared with closely related normal cells)
13) Did the transitivity of sorting out position prove that sorting is caused by adhesiveness, or did it prove that sorting is caused by some one quantitative variable? Would differences in contractile strength have predicted transitivity?
14) Given that there are many different kinds of adhesion molecules, not just one, then if transitivity proves that sorting out is caused by a quantitative variable, does that mean the key variable can't be adhesiveness?
15) Takiechi and Steinberg proved that cells that have more cadherins (cell-cell adhesion proteins) sort out internal to cells with fewer cadherin molecules. That proves that sorting can be caused by having more adhesion; but does it prove that is the only way cell sorting can be produced?
16) Do the observations from Heisenberg's lab disprove the DAH, at least for fish embryo cells?
17) Do you agree with Trinkaus' conclusion that if retinal cells sort out from heart cells, even though they never normally come into contact, therefore cell sorting can't teach us anything about normal embryonic development?
18) Notice the irony that physicists (C.-P. Heisenberg and his collaborators) have published research papers supporting differential contraction over differential adhesion based on force measurements made with an atomic force microscope, without commenting on the relative validity of the thermodynamic dispute between Steinberg and Harris.
19) The Gershman, Drumm and Culp paper (Mentioned above; J. Cell Biology vol. 68 pp 276-286) has only been cited 16 times [six of the 16 are citations by Gershman himself, and one of them is by Barbara Danowski and me] even though it has the most medical relevance of any paper on cell sorting. Apparently, Steinberg never cited Gershman.
20) Why are physicists much faster than biologists in deciding who is correct in disagreements about fundamental issues? Or are physicists always faster? Disagreements about quantum theory lasted decades. Maybe they are just more decisive?
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