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Embryonic tissues as living liquids: A thermodynamic dexcent from organ to tissue to cell to molecule

Malcolm S. Steinberg, Princeton University

During embryonic development, sheets of tissue flow, one over another, and segregate from each other as they differentiate into the body's various tissues and organs. In the 1960s, we conducted behavioral analyses demonstrating that these rearrangements of tissues mimic, in detail, those of mutually immiscible liquids, whose molecules interact with different energies and rearrange to minimize global binding free energy. This requires that, of two immiscible liquids, the one of lower surface tension must tend to spread over its partner. Our "Differential Adhesion Hypothesis" proposed that the motile and mutually adhesive cells of "liquid tissues" do the same, intercellular adhesions playing the same role as intermolecular attractions in non-living liquids. This talk will describe recent experiments in which tissue's true surface tensions are measured and compared with their mutual spreading behavior and in which cell lines are genetically engineered to express specific adhesion molecules (cadherins) in measured quantities which are then related to the surface tensions of the tissues they constitute. From these data, the first molar binding energies of cadherins under physiological conditions are calculated. Those values are extraordinary and in turn suggest an explanation for the hitherto mysterious role of the cell's acting "cytoskeleton" in regulating intercellular adhesion.

 

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